doi: 10.1161/hh1601.095598
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Review |
Phospholipase A2 in Vascular Disease
From AstraZeneca R&D (E.H.-C., G.C.), Cell Biology and Biochemistry, Mölndal; Wallenberg Laboratory (E.H.-C., G.C., H.P.), Göteborg University, Sweden; and Wihuri Research Institute (K.O., P.K.), Helsinki, Finland.
Correspondence to Eva Hurt-Camejo, Cell Biology and Biochemistry, AstraZeneca, R&D, S-431 83, Mölndal, Sweden. E-mail Eva.Hurt-Camejo{at}astrazeneca.com
 |
Abstract |
|---|
 Top Abstract IntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
Secretory phospholipase A2 (PLA2) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA2 can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA2 can hydrolyze lipoproteins. The PLA2-modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA2-modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA2, promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA2-modified lipoproteins themselves or by albumin, into the arterial cells, which then undergo functional alterations. This may, in turn, lead to specific changes in the extracellular matrix, which increase the retention and accumulation of lipoproteins within the matrix. In the present article, we discuss the possible actions of PLA2 enzymes, especially PLA2-IIA, in the arterial wall during atherogenesis.
Key Words: atherosclerosis • inflammation • cytokines • lipases • lysophospholipids
|
Introduction |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
Phospholipase A2 (PLA2) is an enzyme that hydrolyzes the sn-2 ester bond in the glyceroacyl phospholipids present in lipoproteins and cell membranes, forming nonesterified fatty acids (NEFAs) and lysophospholipids.1 These products may act either as intracellular second messengers or be further metabolized into mediators of a broad range of cellular processes.2–8 This review is motivated by evidence suggesting that the PLA2 activity present in arterial intima-media and in plasma may be involved in atherogenesis.9 In vivo and in vitro results indicate that, in the arterial wall, PLA2 may hydrolyze the phospholipids of the apolipoprotein (apo) B-100–containing lipoproteins retained in the arterial intima.10–15 The products of this hydrolysis, NEFAs and lysophospholipids, can trigger a variety of proinflammatory actions that lead to atherosclerotic plaque development.16–19 Furthermore, PLA2-modified apoB-100 lipoproteins, which are more susceptible to further enzymatic and nonenzymatic modifications, induce accumulation of intracellular lipids in macrophages and bind strongly to extracellular matrix proteoglycans.20–23 In addition, PLA2 can induce aggregation and fusion of the matrix-bound lipoproteins and so further increase their binding strength to the matrix proteoglycans.24 Thus, in atherosclerosis-prone regions of arteries, PLA2 may contribute to both intra- and extracellular accumulation of apoB-100 lipoproteins. On the other hand, circulating PLA2 activity can modify LDL and HDL in plasma and may contribute to the generation of an atherogenic lipoprotein profile.25–27 Recent clinical studies indicate that an elevated plasma level of PLA2 is a strong independent risk factor for coronary heart disease.28–30 Whether this is associated with the proatherogenic mechanisms of PLA2 activity in plasma or with their actions in the arterial wall remains to be elucidated. The hypothesis of the potential involvement of sPLA2-IIA in the pathogenesis of atherosclerosis is reinforced by in vivo data showing that transgenic mice expressing human sPLA2-IIA have increased susceptibility to atherosclerosis.14,26 The PLA2-induced changes in the physicochemical properties of circulating lipoproteins, mainly LDL, and their implications for atherogenesis were reviewed recently.31 In the present review, we discuss new evidence for potential atherogenic mechanisms of PLA2 activity in the arterial wall.
|
The Family of PLA2 |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
The PLA2 family comprises a rapidly growing group of intracellular and secreted enzymes. The mammalian secretory PLA2 (sPLA) isoforms comprise the groups named IB, IIA, IIC, IID, IIE, IIF, V, X, and XII, along with a novel member, the type III sPLA recently cloned from human liver.32,33 Interestingly, human groups IIA, IIC, IID, IIE, IIF, and group V genes are clustered on chromosome 1, whereas the structurally more distant IB, X, XII, and III lie on different chromosomes.33 All sPLAs, except type III, have in common a low molecular weight, 13 to 16 kDa, several disulfide bridges, a Ca2+-dependent catalytic mechanism, and a well-conserved overall three-dimensional structure.32,34,35
Mammalian sPLA2 appears to be implicated in a variety of physiological and pathological processes. These include lipid digestion, release of potent lipid mediators in response to cytokines stimulus,36 cell proliferation,37 control of virus and bacterial infection,38,39 removal of apoptotic or injured cells,40,41 phospholipid repair, lipoprotein catabolism,25,27,42,43 tumorigenesis, and inflammation (for reviews, see Uhl et al44).
|
sPLA2-IIA in the Arterial Wall |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
sPLA2-IIA was first isolated and purified from rheumatoid synovial fluid and is often referred to in the literature as synovial fluid sPLA2. The enzyme was cloned in 1989, and the crystal structure at 2.2 Å was established in 1991.45,46 SPLA2-IIA contains seven disulfide bridges, which confer a rigid structure and resistance to pH and to thermal and proteolytic denaturation. The protein has 23 cationic amino acid residues, arginine (Arg) and lysine (Lys), which contribute to its high positive charge (pI=10.5). Specific cationic residues on its surface, among them Arg-7, Lys-10, and Lys-16, contribute significantly to the interfacial adsorption of the enzyme to the surface phospholipid monolayers of cell membranes, lipoproteins, and aggregated phospholipids.47 Furthermore, the positively charged regions may facilitate interaction with the negatively charged sulfated glycosaminoglycans of proteoglycans on the cell membranes and the extracellular matrix. These interactions with matrix and cell-surface proteoglycans help to localize the enzyme at such sites and to modulate its activity.23,48,49
In nonatherosclerotic human arteries, sPLA2-IIA is mainly associated with the smooth muscle cells of the media, whereas in atherosclerotic plaques the enzyme is also found in macrophage-rich regions, in the acellular lipid core of atheromas, and in the extracellular matrix of the diseased intima in association with collagen fibers.15,50 Immunohistochemical studies performed by several research groups show that sPLA2-IIA is found at all stages of atherosclerotic lesion development.15,50–55 Cytoplasmic PLA2 (group IV) is also present in atherosclerotic lesions containing macrophages. However, the activity of sPLA2-IIA is more prominent than that of the cytoplasmic enzyme in the same human plaque.52 In summary, immunohistochemical studies show that sPLA2-IIA is present in normal arteries, and that, in early and late atherosclerotic lesions, its extracellular distribution and level of cell expression is increased, suggesting that the enzyme is implicated in atherogenesis.15,52,53
Most studies on sPLA2-IIA expression in vascular cells have been performed with rat smooth muscle cells.56 Although some of these results can be extrapolated to human arterial smooth muscle cells, recent studies suggest that regulation of sPLA2-IIA gene expression is cell- and species-specific.57,58 We reported recently that expression of both sPLA2-IIA mRNA and protein by human arterial smooth muscle cells from the aorta and the coronary and uterine arteries requires conditions that promote cell differentiation in vitro.58 These in vitro results agree with immunohistochemical data showing that, in arteries, the main source of sPLA2-IIA is smooth muscle cells.15,55 Electron microscopy shows that sPLA2-IIA is stored intracellularly inside vesicles close to the smooth muscle cell membrane.50 Cytokines, in vitro, differentially modulate cell secretion and mRNA levels of sPLA2-IIA. Thus, interferon-
(IFN-) increases the expression of mRNA and sPLA2-IIA protein secretion 2- to 6- fold, and, after addition of IFN-, this effect lasts up to 48 hours. On the other hand, tumor necrosis factor-
(TNF-) stimulates sPLA2-IIA secretion for only 4 hours, without detectable changes in mRNA levels. Interestingly, a similar effect of TNF- is seen in sPLA2-IIA transgenic mice.39,59 Interleukin-10 (IL-10), an anti-inflammatory cytokine, downregulates IFN-, but not TNF-, induction of sPLA2-IIA secretion. In contrast to what was reported with rat smooth muscle cells, interleukin-1ß (IL-1ß) is not a strong inducer of sPLA2-IIA in human arterial smooth muscle cells. Colocalization of sPLA2-IIA with the mRNA transcript for IFN-, IL-1ß, and TNF- in human atherosclerotic lesions supports a possible in vivo involvement of these cytokines in the regulation of sPLA2-IIA gene expression and protein secretion in atherosclerotic plaques.54
Cytokines acting on tissues may also indirectly regulate the circulating levels of sPLA2-IIA in plasma. SPLA2-IIA is an acute-phase reactant and, in diseases that involve systemic inflammation such as sepsis, rheumatoid arthritis,60 and cardiovascular disease,30,61 its plasma levels are increased. Hepatocytes synthesize and secrete this enzyme in response to cytokines such as IL-6, TNF-, and IL-1ß,62 but not IFN-.58 In addition, peritoneal injections of IL-6, TNF-, and IL-1ß increase plasma levels of sPLA2-IIA in transgenic mice expressing the gene of human sPLA2-IIA.39,59 Together, these data suggest that hepatocytes and arterial smooth muscle cells may contribute to the bulk of circulating sPLA2-IIA in plasma modulated by systemic inflammatory conditions. This hypothesis is illustrated in Figure 1.
|
The presence of active sPLA2-IIA in plasma suggests that it may hydrolyze the surface phospholipid monolayer of plasma lipoproteins. A high plasma level of sPLA2-IIA correlates positively with C-reactive protein (CRP) levels and predicts coronary events due to atherosclerosis.28,30,61,63 This association is independent of other established risk factors.28 Furthermore, positive correlations between sPLA2-IIA and soluble adhesion molecules, CRP, and antibody titers to oxidized LDL in plasma of hypercholesterolemic patients were recently reported.64,65 In vitro hydrolysis of LDL phospholipids makes the lipoproteins particles more susceptible to oxidative modification.16,66 Thus, a similar process in plasma may generate oxidation-susceptible LDL and a possible circulating antigen. The clinical studies cited suggest that sPLA2-IIA in plasma may serve as another inflammatory marker for cardiovascular diseases, similar to CRP, serum amyloid A protein (SAA), soluble adhesion molecules, IL-6, and circulating oxidized LDL.67,68
|
Possible Atherogenic Actions of sPLA2-IIA |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
The basic tenet of the response-to-retention hypothesis of atherosclerosis is that the lesions are the response of the arterial tissue to local accumulation and modification of apoB-100–containing lipoproteins in the intima of the arterial wall.69–71 Specific interactions of apoB-100–containing lipoproteins with chondroitin-sulfate proteoglycans such as versican or decorin appear to be important mechanisms contributing to their retention and modification.70 This early phenomenon is documented in ultrastructural studies showing accumulation of aggregated and fused lipoprotein particles in the subendothelial extracellular matrix before macrophages appear.72 Furthermore, early lesions in human aortas from fetuses of hypercholesterolemic women frequently contain LDL and oxidized LDL in the absence of monocyte-macrophages.73 Together, these observations suggest that modification of the lipoproteins retained in the extracellular matrix may precede lesion formation. In the arterial intima, there are proteolytic and lipolytic enzymes and pro-oxidant conditions capable of modifying the LDL retained in the extracellular matrix.15,74–78 Interestingly, the binding strength of LDL particles to extracellular matrix proteoglycans is increased by proteolytic and lipolytic modifications, whereas the binding strength of oxidized LDL is decreased.79 Indirect evidence indicates that once apoB-100 lipoproteins are in the intima, hydrolysis of phosphatidylcholine by PLA2-like activity takes place rapidly.10–12 In addition, the concentration of lysophospholipids in rabbit atherosclerotic aorta is reported to be higher than in control tissue.13 Furthermore, active sPLA2-IIA isolated from human arterial tissue is able to hydrolyze the phospholipids in LDL.15
In the arterial wall, sPLA2-IIA may exert proatherogenic effects by the three main mechanisms illustrated in Figure 2. First, it may induce release of relatively high concentrations of lipid mediators such as NEFAs, oxidized NEFAs, and lysophospholipids, which may affect the function and properties of vascular cells at sites of apoB-100 lipoprotein accumulation.7,22 Second, sPLA2-IIA may modify apoB-100 lipoproteins to a more atherogenic form by increasing their binding affinity toward proteoglycans and also by making the PLA2-treated lipoproteins more susceptible to further oxidative and enzymatic modifications.16,42,66 Third, the enzyme can also contribute to lipoprotein accumulation by inducing aggregation and fusion of the proteoglycan-bound apoB-100 lipoproteins.31,79,80 Treatment of LDL with sPLA2-IIA in the presence of physiological albumin concentration leads to the formation of small dense LDL particles with increased affinity for glycosaminoglycans and proteoglycans.23 As discussed above, this may take place in the plasma31 or in the arterial wall, where extracellular sPLA2 can hydrolyze the phospholipids on the lipoprotein particles. Because PLA2-treated LDL particles have an increased affinity for extracellular proteoglycans, their residence time in the arterial wall is likely to increase. This provides the possibility for further modifications of these particles. In fact, PLA2-treated LDL particles are more susceptible to lipid peroxidation,66 generation of bioactive phospholipids,26 and hydrolysis by secretory sphingomyelinase.81 In addition, treatment of LDL with PLA2 facilitates sphingomyelinase-induced aggregation and fusion of LDL particles.82 PLA2 can also directly induce aggregation and fusion of LDL particles: treatment of proteoglycan-bound LDL with sPLA2-IIA leads to aggregation and subsequent fusion of the modified LDL particles.24 Interestingly, PLA2 induces fusion of LDL particles only if the particles are bound to glycosaminoglycans either before, during, or after lipolysis.83 The interaction between LDL and glycosaminoglycans can apparently overcome the rigidifying effect of PLA2-induced hydrolysis on LDL particles.79 Thus, it can be hypothesized that if the small dense LDL particles generated by the action of sPLA2-IIA either in plasma or in the arterial intima bind to arterial proteoglycans, this interaction will then trigger aggregation and fusion of the bound LDL particles. Because each aggregate or fused particle contains several copies of apoB-100, it is not surprising that the aggregated/fused particles bind to proteoglycans even more tightly than do the small dense PLA2-treated LDL.82 Moreover, as the modified LDL particles aggregate or fuse, the capacity of arterial proteoglycans to bind LDL increases.24 Thus, aggregation and fusion of LDL particles in the arterial intima are likely to lead to accumulation of LDL-derived lipid particles within the extracellular matrix. Such progressive deposition of lipid within the extracellular matrix of the arterial intima is a central feature of atherogenesis and thus makes the arterial sPLA2-IIA a strong candidate as one of the key enzymes acting in the extracellular space during the development of atherosclerotic lesions. These proatherogenic mechanisms may be potentiated by the colocalization of sPLA2-IIA and apoB-100 lipoproteins with extracellular matrix proteoglycans in the intima. It should be stressed that the total hydrolysis of the phosphoglycerides from one LDL particle may generate more than 500 molecules of lysophospholipids and NEFAs. Thus, at sites of retention of apoB-100 lipoproteins in the arterial intima, NEFAs and lysophospholipids may reach high local concentrations. These bioactive products can induce different proatherogenic cellular processes and cell membrane perturbation. Human arterial smooth muscle cells exposed to albumin-bound NEFAs upregulate the synthesis of matrix proteoglycans.19 This results in a matrix that has a higher affinity for LDL, suggesting the possibility of a noxious cycle in which sPLA2-IIA products from apoB-100 lipoproteins entrapped in the intima trigger matrix changes, which, in turn, lead to further accumulation of lipoproteins. Peroxisome proliferator-activated receptor- (PPAR-) agonists oppose this action of NEFAs, suggesting that the improved metabolism of NEFAs downregulates the increase in matrix synthesis in vivo.
|
|
Molecular Basis and Effects of the sPLA2-IIA Interaction With Arterial Proteoglycans |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
Extracellular sPLA2-IIA is associated with collagen fibers and proteoglycans in atherosclerotic lesions from human coronary arteries.50 The enzyme binds to collagen via a specific interaction with decorin, a proteoglycan containing the chondroitin and dermatan sulfate chains of the serine- and leucine-rich protein (SLRP) family that is associated with collagen fibers.84 In physiological salt and pH conditions, the enzyme is able to interact with both the glycosaminoglycan moiety and the core protein of decorin. In addition, sPLA2-IIA binds to the major proteoglycans of the arterial intima, versican and biglycan. However, with these molecules, the interaction takes place only through the glycosaminoglycan moiety. These associations with versican, biglycan, and decorin increase the hydrolytic activity of sPLA2-IIA toward the phospholipids on LDL or in micelles.23,48 Together with the remarkable stability of the enzyme, these results suggest that sPLA2-IIA could remain sequestered in an active form for prolonged periods in the extracellular environment of the arterial intima. This may be important for the normal functioning of the enzyme, but when it is secreted in excess, may potentiate its proatherogenic actions.
|
Other PLA2 Enzymes of Interest in Atherosclerosis |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
Other sPLA2 enzymes may have relevance for the physiology and pathology of the arterial wall. Plasma platelet-activating factor (PAF) acetylhydrolase (PAF-AH or group VII) is a serine lipase that hydrolyzes the sn-2 ester bond of PAF and thus attenuates its bioactivity. Some experimental and clinical studies suggest that PAF acetylhydrolase has anti-inflammatory properties.85 In contrast, this enzyme was suggested to be a proinflammatory agent because of its capacity to hydrolyze oxidized phospholipids releasing lysophospholipids and oxidized fatty acids from free radical–oxidized lipoproteins retained in the arterial intima.86 PAF-AH circulating in plasma is associated with lipoproteins, mainly LDL, and, because of its PLA2 property, it is also known as lipoprotein-associated PLA2.87 In addition, this enzyme is expressed by macrophages in human and rabbit atherosclerotic lesions.88 Recently, lipoprotein-associated PLA2 was reported to be an independent risk factor for coronary heart diseases in hypercholesterolemic patients.29 Furthermore, inhibition of the enzyme slows down atherogenesis in LDL receptor–defective Watanabe rabbits.86 This suggests that lipoprotein-associated PLA2 could become a new target for therapeutic antiatherosclerotic intervention.86
There are no studies that could help us to conclude which of these two phospholipases, sPLA2-IIA or the lipoprotein-associated enzyme, has the greater potential for atherogenesis. However, compared with the lipoprotein-associated PLA2, sPLA2-IIA hydrolyzes intact as well as oxidized phospholipids, thus generating NEFAs, oxidized NEFAs, and lysophospholipids from a broader spectrum of substrates. In addition, its expression in the mouse increases the susceptibility to atherosclerosis and its plasma levels predict coronary events in patients with well-defined atherosclerosis. Therefore, sPLA2-IIA may also be a potential target for therapeutic antiatherogenic agents. In vivo studies in models of atherosclerosis with specific inhibitors of each enzyme will be necessary to evaluate their relative relevance for the disease in vivo.
Although not yet directly implicated in arterial disease, the group V and group X sPLA2 enzymes are expressed in macrophages and mast cells (group V) and in spleen and thymus (group X),89–91 and a novel sPLA2, group XII, is found in stimulated type 2 helper T cells.92 Therefore, these enzymes may be prominent at sites where macrophages, lymphocytes, and mast cells accumulate in atherosclerotic lesions. Groups V and X are more efficient than sPLA2-IIA in hydrolyzing phosphatidylcholine vesicles and the outer plasma membrane of intact mammalian cells.93 Thus, their capacity to release fatty acids and lysophospholipids, which in turn induce cellular eicosanoid production, may also be higher than that of sPLA2-IIA.90,93 The presence of tryptophan and less basic residues in the interface-binding region of these enzymes appears to contribute to their efficient hydrolysis of cell-membrane phospholipids.34 However, the possible involvement of sPLA2-V, sPLA2-X, and sPLA2-XII and their potential overlapping function with sPLA2-IIA in sustaining a chronic inflammation in atherogenesis remains to be studied.
In addition to the secretory phospholipases mentioned above, an endothelial lipase (EL) was discovered recently.94,95 EL belongs to the family of triglyceride lipases. However, in contrast to other lipases, EL has substantial phospholipase activity and lipoprotein phospholipids are its major substrate.94,95 EL is synthesized by macrophages, and its expression by coronary artery endothelial cells is upregulated by inflammatory cytokines.96 Thus, this enzyme provides the arterial intima with another regulated lipolytic mechanism for local release of fatty acids and lysophospholipids from lipoproteins that may influence atherogenesis.97
|
Future Directions |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
For many years, researchers and the pharmaceutical industry have studied the possibility of using inhibitors of sPLA2 to treat proinflammatory conditions. However, new knowledge about the existence of many types of sPLA2 highlights the need for specific inhibitors. The recent elucidation of the human and other genomes may add new PLA2 genes to this already growing family.32 This information, combined with the use of proteomics and genetically manipulated mouse models of atherosclerosis, should increase our knowledge of the specific and potentially overlapping roles of individual phospholipases as mediators of physiological and pathological processes. Hopefully, such understanding will enable the development of specific agents aimed at decreasing the potential contribution of individual secretory phospholipases to atherosclerotic disease.
|
Acknowledgments |
|---|
This work was supported by the Medical Research Council (project No. 12129 to E.H.-C.), the Swedish Heart and Lung Foundation (project No. 41224 to E.H.-C.), and AstraZeneca R&D, Mölndal, Sweden. The authors wish to thank Lennart Storlien for his comments on the manuscript.
Received March 12, 2001; accepted July 3, 2001.
|
References |
|---|
|
TopAbstractIntroductionThe Family of PLA2sPLA2-IIA in the Arterial...Possible Atherogenic Actions of...Molecular Basis and Effects...Other PLA2 Enzymes of...Future DirectionsReferences |
|---|
1. Dennis EA, Six DA. The expanding superfamily of phospholipase A2 enzymes: classification and characterization. Biochim Biophys Acta. . 2000; 1488: 1–19.[Medline] [Order article via Infotrieve]
2. Pruzanski W, Vadas P. Phospholipase A 2: a mediator between proximal and distal effectors of inflammation. Immunol Today. . 1991; 12: 143–146.[Medline] [Order article via Infotrieve]
3. Marcus AJ, Hajjar DP. Vascular transcellular signaling. J Lipid Res. . 1993; 34: 2017–2031.[Abstract]
4. Evangelou AM. Platelet-activating factor (PAF): implications for coronary heart and vascular diseases. Prostaglandins Leukot Essent Fatty Acids. . 1994; 50: 1–28.[Medline] [Order article via Infotrieve]
5. Moolenaar WH, Kranenburg O, Postma FR, Zondag GCM. Lysophosphatidic acid: G-protein signalling and cellular responses. Curr Opin Cell Biol. . 1997; 9: 168–173.[Medline] [Order article via Infotrieve]
6. Henning B, Meerarani P, Ramadass P, Watkins BA, Toborek M. Fatty acid-mediated activation of vascular endothelial cells. Metabolism. . 2000; 49: 1006–1013.[Medline] [Order article via Infotrieve]
7. Camejo G, Hurt-Camejo E, Olsson U, Bondjers G. Lipid mediators that modulate the extracellular matrix structure and the function in vascular cells. Curr Atheroscler Rep. . 1999; 1: 142–149.[Medline] [Order article via Infotrieve]
8.
Morimoto M, Kume N, Muyamoto S, Ueno Y, Kataoka H, Minami M, Hayashida K, Hashimoto N, Kita T. Lysophosphatidylcholine induces early growth response factor-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells. Arterioscler Thromb. . 2001; 21: 771–776.
9.
Kovanen PT, Pentikäinen MO. Secretory group II phospholipase A2: a newly recognized acute-phase reactant with a role in atherogenesis. Circ Res. . 2000; 86: 610–612.
10. Camejo G, Hurt E, Romano M. Properties of lipoprotein complexes isolated by affinity chromatography from human aorta. Biomed Biochim Acta. . 1985; 44: 389–401.[Medline] [Order article via Infotrieve]
11.
Daugherty A, Zweifel BS, Sobel BE, Schonfeld G. Isolation of low density lipoprotein from atherosclerotic vascular tissue of Watanabe heritable hyperlipidemic rabbits. Arteriosclerosis. . 1988; 8: 768–777.
12. Tailleux A, Torpier G, Caron B, Fruchart J-C, Fievet C. Immunological properties of ApoB-containing lipoprotein particles in human atherosclerotic arteries. J Lipid Res. . 1993; 34: 719–728.[Abstract]
13. Keaney JF, Xu A, Cunningham D, Jackson T, Frei B, Vita JA. Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J Clin Invest. . 1995; 95: 2520–2529.
14.
Ivandic B, Castellini LW, Wang X-P, Qiao J-H, Mehrabian M, Navab M, Fogelman AM, Grass DS, Swanson ME, de Beer MC, de Beer F, Lusis AJ. Role of group II secretory phospholipase A2 in atherosclerosis, 1: increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A2. Arterioscler Thromb Vasc Biol. . 1999; 19: 1284–1290.
15.
Hurt-Camejo E, Anderssen S, Standal R, Rosengren B, Sartipy P, Stadberg E, Johansen B. Localization of non pancreatic secretory phospholipase A2 in normal and atherosclerotic arteries: activity of the isolated enzyme on low density lipoprotein. Arterioscler Thromb Vasc Biol. . 1997; 17: 300–309.
16. Sparrow CP, Parthasarathy S, Steinberg D. Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J Lipid Res. . 1988; 29: 745–753.[Abstract]
17. Gimbrone MAJ. Vascular endothelium: an integrator of pathophysiological stimuli in atherogenesis. Ann NY Acad Sci. . 1995; 748: 122–132.[Medline] [Order article via Infotrieve]
18. Berliner J, Leitinger N, Watson A, Huber J, Fogelman A, Navab M. Oxidized lipids in atherogenesis: formation, destruction and action. Thromb Haemost. . 1997; 78: 195–199.[Medline] [Order article via Infotrieve]
19. Olsson U, Bondjers G, Camejo G. Fatty acids modulate the composition of extracellular matrix in cultured human arterial smooth muscle cells by altering the expression of genes for proteoglycan core proteins. Diabetes. . 1999; 48: 616–622.[Abstract]
20. Menschikowski M, Lattke P, Bergmann S, Jaross W. Exposure of macrophages to PLA2-modified lipoproteins leads to cellular lipid accumulations. Anal Cell Pathol. . 1995; 9: 113–121.[Medline] [Order article via Infotrieve]
21.
Hurt-Camejo E, Olsson U, Wiklund O, Bondjers G, Camejo G. Cellular consequences of the association of apoB lipoproteins with proteoglycans. Arterioscler Thromb Vasc Biol. . 1997; 17: 1011–1017.
22. Hurt-Camejo E, Camejo G. Potential involvement of type II phospholipase A2 in atherosclerosis. Athersoclerosis. . 1997; 132: 1–8.[Medline] [Order article via Infotrieve]
23.
Sartipy P, Bondjers G, Hurt-Camejo E. Phospholipase A 2 type II binds to extracellular matrix biglycan: modulation of its activity on LDL by colocalization in glycosaminoglycan matrixes. Arterioscler Thromb Vasc Biol. . 1998; 18: 1934–1941.
24.
Hakala JK, Öörni K, Pentikäinen MO, Hurt-Camejo E, Kovanen PT. Lipolysis of LDL by human secretory phospholipase A2 induces particle fusion and enhances the retention of LDL to human aortic proteoglycans. Arterioscler Thromb Vasc Biol. . 2001; 21: 1053–1058.
25. de Beer FC, de Beer MC, van der Westhuyzen DR, Castellani LW, Lusis AJ, Swanson ME, Grass DS. Secretory non-pancreatic phospholipase A2: influence on lipoprotein metabolism. J Lipid Res. . 1997; 38: 2232–2239.[Abstract]
26.
Leitinger N, Watson AD, Hama SY, Ivandic B, Qiao J-H, Huber J, Faull KF, Grass DS, Navab M, Fogelman AM, de Beer FC, Lusis AJ, Berliner JA. Role of group II secretory phospholipase A2 in atherosclerosis, 2: potential involvement of biologically active oxidized phospholipids. Arterioscler Thromb Vasc Biol. . 1999; 19: 1291–1298.
27. Sartipy P, Hurt-Camejo E. Modification of plasma lipoproteins by group IIA phospholipase A2: possible implications for atherogenesis. Trends Cardiovasc. . 1999; 9: 232–238.
28.
Kugiyama K, Ota Y, Takazoe K, Moriyama Y, Kawano H, Miyao Y, Sakamoto T, Soejima H, Ogawa H, Doi H, Sugiyama S, Yasue H. Circulating levels of secretory type II phospholipase A2 predict coronary events in patients with coronary artery disease. Circulation. . 1999; 100: 1280–1284.
29.
Packard C, O’Reilly DSJ, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M, Wilkinson FE, Rumley A, Lowe GDO. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. N Engl J Med. . 2000; 343: 1148–1154.
30. Porela P, Pulkki K, Voipio-Pulkki L-M, Pettersson K, Leppänen V, Nevalainen TJ. Level of circulating phospholipase A2 in prediction of the prognosis of patients with suspected myocardial infarction. Basic Res Cardiol. . 2000; 5: 413–417.
31. Hurt-Camejo E, Camejo G, Sartipy P. Phospholipase A 2 and small, dense low-density lipoprotein. Curr Opin Lipidol. . 2000; 11: 465–471.[Medline] [Order article via Infotrieve]
32. Six DA, Dennis EA. The expanding superfamily of phospholipase A2 enzymes: classification and characterization. Biochim Biophys Acta. . 2000; 1488: 1–19.
33.
Gelb MH, Valentin E, Ghomashchi F, Lazdunski M, Lambeau G. Cloning and recombinant expression of a structurally novel human secreted phospholipase A2. J Biol Chem. . 2000; 275: 39823–39826.
34. Gelb MH, Cho W, Wilton DC. Interfacial binding of secreted phospholipases A2: more than electrostatics and a major role for tryptophan. Curr Opin Struct Biol. . 1999; 9: 428–432.[Medline] [Order article via Infotrieve]
35. Valentin E, Lambeau G. Increasing molecular diversity of secreted phospholipases A2 and their receptors and binding proteins. Biochim Biophys Acta. . 2000; 1488: 59–70.[Medline] [Order article via Infotrieve]
36.
Murakami M, Shimbara S, Kambe T, Kuwatat H, Winstead MV, Tischfield JA, Kudo I. The functions of five distinct mammalian phospholipase A2 in regulating arachidonic acid release. J Biol Chem. . 1998; 273: 14411–14423.
37.
Hernández M, Burillo SL, Crespo MS, Nieto ML. Secretory phospholipase A2 activates the cascade of mitogen-activated protein kinases and cytosolic phospholipase A2 in the human astrocytoma cell line 1321N1. J Biol Chem. . 1998; 273: 606–612.
38. Fenard D, Lambeau G, Valentin E, Lefebvre J-C, Lazdunski M, Doglio A. Secreted phospholipases A2, a new class of HIV inhibitors that block virus entry into host cells. J Clin Invest. . 1999; 104: 611–618.[Medline] [Order article via Infotrieve]
39.
Laine VJO, Grass DS, Nevalainen TJ. Protection of group II phospholipase A2 against Staphylococcus aureus. J Immunol. . 1999; 162: 7402–7408.
40. Hack CE, Wolbink G-J, Schalkwijk C, Speijer H, Hermens WT, van den Bosch H. A role for secretory phospholipase A2 and C-reactive protein in the removal of injured cells. Immunol Today. . 1997; 18: 111–115.[Medline] [Order article via Infotrieve]
41.
Cummings BS, Mchowat J, Schellmann RG. Phospholipase A 2 in cell injury and death. J Pharmacol Exp Ther. . 2000; 294: 793–799.
42.
Sartipy P, Camejo G, Svensson L, Hurt-Camejo E. Phospholipase A 2: modification of low density lipoproteins forms small, high density particles with increased affinity for proteoglycans and glycosaminoglycans. J Biol Chem. . 1999; 274: 25913–25920.
43. Menschikowski M, Eckey R, Pietsch J, Auffenanger J, Kumpf R, Nelz P, Jaross W. Expression of human secretory group IIA phospholipase A2 is associated with reduced concentrations of plasma cholesterol in transgenic mice. Inflammation. . 2000; 24: 227–237.
44. Uhl W, Nevalainen TJ, Büchler MW, eds. Phospholipase A2: Basic and Clinical Aspects in Inflammatory Diseases. Basel, Switzerland: Karger; 1997.
45.
Kramer RM, Hession C, Johansen B, Hayes G, McGray P, Chow EP, Tizard R, Pepinsky RB. Structure and properties of a human non-pancreatic phospholipase A2. J Biol Chem. . 1989; 264: 5768–5775.
46. Wery JP, Schevitz RW, Clawson DK, Bobbitt JL, Dow ER, Gamboa G, Goodson T, Hermann RB, Kramer RM, McClure DB, Mihelich ED, Putman JE, Sharp JD, Stark DH, Teater C, Warrick MW, Jones ND. Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2 A resolution. Nature. . 1991; 352: 79–82.[Medline] [Order article via Infotrieve]
47. Snitko Y, Koduri RS, Han SK, Othman R, Baker SF, Molini BJ, Wilton DC, Gelb MH, Cho W. Mapping the interfacial binding surface of human secretory group IIa phospholipase A2. Biochemistry. . 1997; 36: 14325–14333.[Medline] [Order article via Infotrieve]
48.
Sartipy P, Johansen B, Camejo G, Rosengren B, Bondjers G, Hurt-Camejo E. Binding of human phospholipase A2 type II to proteoglycans: differential effect of glycosaminoglycans on enzyme activity. J Biol Chem. . 1996; 271: 26307–26314.
49.
Murakami M, Kambe T, Shimbra S, Yamamoto S, Kuwata H, Kudo I. Functional association of type IIA secretory phospholipase A2 with the glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan in the cyclooxygenase-2-mediated delayed prostanoid-biosynthetic pathway. J Biol Chem. . 1999; 274: 29927–29936.
50.
Romano M, Romano E, Björkerud S, Hurt-Camejo E. Ultrastructural localization of secretory type II phospholipase A2 in atherosclerotic and nonatherosclerotic regions of human arteries. Arterioscler Thromb Vasc Biol. . 1998; 18: 519–525.
51. Menschikowski M, Kasper M, Lattke P, Schiering A, Schiefer S, Stockinger H, Jaross W. Secretory group II phospholipase A2 in human atherosclerotic plaques. Atherosclerosis. . 1995; 118: 173–181.[Medline] [Order article via Infotrieve]
52.
Elinder LS, Dumitrescu A, Larsson P, Hedin U, Fostergård J, Claesson H-E. Expression of phospholipase A2 isoforms in human normal and atherosclerotic arterial wall. Arterioscler Thromb Vasc Biol. . 1997; 17: 2257–2263.
53. Schiering A, Menschikowski M, Mueller E, Jaross W. Analysis of secretory group II phospholipase A2 expression in human aortic tissue in dependence on the degree of atherosclerosis. Atherosclerosis. . 1999; 144: 73–78.[Medline] [Order article via Infotrieve]
54.
Menschikowski M, Rosner-Schiering A, Eckey R, Mueller E, Koch R, Jaross W. Expression of secretory group IIA phospholipase A2 in relation to the presence of microbial agents, macrophage infiltrates, and transcripts of proinflammatory cytokines in human aortic tissues. Arterioscler Thromb Vasc Biol. . 2000; 20: 751–762.
55.
Sartipy P, Johansen B, Gåsnik K, Hurt-Camejo E. Molecular basis for the association of group IIA phospholipase A2 and decorin in human atherosclerotic lesions. Circ Res. . 2000; 86: 707–714.
56. Pfeilschifter J, Walker G, Kunz D, Pignat W, van den Bosch H. Control of phospholipase A2 gene expression. In: Uhl W, Nevalainen TJ, Büchler MW, eds. Phospholipase A2: Basic and Clinical Aspects in Inflammatory Diseases. Basel, Switzerland: Karger; 1997: 31–37.
57. Andreani M, Olivier JL, Berenbaum F, Raymondjean M, Béréziat G. Transcriptional regulation of inflammatory secreted phospholipase A2. Biochim Biophys Acta. . 2000; 1488: 149–158.[Medline] [Order article via Infotrieve]
58.
Peilot H, Rosengren B, Bondjers G, Hurt-Camejo E. IFN- induces secretory group IIA phospholipase A2 in human arterial smooth muscle cells: involvement of cell differentiation, STAT-3 activation and modulation by other cytokines. J Biol Chem. . 2000; 275: 22895–22904.
60. Nevalainen TJ. Serum phospholipase A2 in inflammatory diseases. Clin Chem. . 1993; 39: 2453–2459.[Abstract]
61.
Kugiyama K, Ota Y, Kawano H, Soejima H, Ogawa H, Sugiyama S, Doi H, Yasue H. Increase in plasma levels of secretory type II phospholipase A2 in patients with coronary spastic angina. Cardiovasc Res. . 2000; 47: 159–165.
62.
Vadas P, Grouix B, Stefanski E, Wolch M, Pruzanski W, Schroeder J, Gauldie J. Coordinate expression of group II phospholipase A2 and the acute-phase proteins haptoglobin (HP) and 1-anti-chymotrypsin (ACH) by HepG2 cells. Clin Exp Immunol. . 1997; 108: 175–180.[Medline]
[Order article via Infotrieve]
63. Aarsman AJ, Neys FW, van der Helm HA, Kuypers FA, van den Bosch H. Sera of patients suffering from inflammatory diseases contain group IIA but not group V phospholipase A2. Biochim Biophys Acta. . 2000; 1502: 257–263.[Medline] [Order article via Infotrieve]
64.
Hulthe J, Wiklund O, Hurt-Camejo E, Bondjers G. Antibodies to oxidized LDL in relation to carotid atherosclerosis, cell adhesion molecules, and phospholipase A2. Arterioscler Thromb Vasc Biol. . 2001; 21: 269–274.
65. Wiklund O, Hulthe J, Bondjers G, Hurt-Camejo E. Cell adhesion molecules and secretory type II phospholipase A2 in relation to carotid atherosclerosis in patients with hypercholesterolemia. J Intern Med. . 2001; 249: 441–449.[Medline] [Order article via Infotrieve]
66. Neuzil J, Upston JM, Witting PK, Scott KF, Stocker R. Secretory phospholipase A2 and lipoprotein lipase enhance 15-lipoxygenase-induced enzymic and nonenzymic lipid peroxidation in low density lipoproteins. Biochemistry. . 1998; 37: 9203–9210.[Medline] [Order article via Infotrieve]
67.
Ridker PM. Evaluating novel cardiovascular risk factors: can we better predict hearts attacks? Ann Intern Med. . 1999; 130: 933–937.
68.
Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, Van de Werf F. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol. . 2001; 21: 844–848.
69. Camejo G. The interaction of lipids and lipoproteins with the intercellular matrix of arterial tissue: its possible role in atherogenesis. Adv Lipid Res. . 1982; 19: 1–53.[Medline] [Order article via Infotrieve]
70. Camejo G, Hurt-Camejo E, Wiklund O, Bondjers G. Association of apoB lipoproteins with arterial proteoglycans: pathological significance and molecular basis. Atherosclerosis. . 1998; 139: 205–222.[Medline] [Order article via Infotrieve]
71.
Williams KJ, Tabas I. The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol. . 1995; 15: 551–561.
72.
Tamminen M, Mottino G, Qiao JH, Breslow JL, Frank JS. Ultrastructure of early lipid accumulation in apoE-deficient mice. Arterioscler Thromb Vasc Biol. . 1999; 19: 847–853.
73. Napoli C, D’Armiento FP, Mancini FP, Postiglione A, Witzum JL, Palumbo G, Palinski W. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia: intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. . 1997; 100: 2680–2690.[Medline] [Order article via Infotrieve]
74.
Bhakdi S, Dorweiler B, Kirchmann R, Torzewski J, Weise E, Tranum-Jensen J, Walev I, Wieland E. On the pathogenesis of atherosclerosis: enzymatic transformation of human low density lipoprotein to an atherogenic moiety. J Exp Med. . 1995; 182: 1959–1971.
75. Schissel SL, Tweedie-Hardman J, Rapp JH, Graham G, Williams KJ, Tabas I. Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. J Clin Invest. . 1996; 98: 1455–1464.[Medline] [Order article via Infotrieve]
76. Goldberg I. Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res. . 1996; 37: 495–516.
77.
Sugiyama S, Okada Y, Sukhova GK, Virmani R, Heinecke JW, Libby P. Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol. . 2001; 158: 879–891.
78.
Kaartinen M, Penttilä A, Kovanen PT. Mast cells of two types differing in neutral protease composition in the human aortic intima: demonstration of tryptase- and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder regions of atheromas. Arterioscler Thromb Vasc Biol. . 1994; 14: 966–972.
79.
Öörni K, Pentikäinen MO, Ala-Korpela M, Kovanen PT. Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effect on matrix interactions. J Lipid Res. . 2000; 41: 1703–1713.
80. Pentikäinen MO, Öörni K, Ala-Korpela M, Kovanen PT. Modified LDL -trigger of atherosclerosis and inflammation in the arterial intima. J Intern Med. . 2000; 247: 359–370.[Medline] [Order article via Infotrieve]
81.
Schissel SL, Jiang X-C, Tweedie-Hardman J, Jeong T-S, Hurt-Camejo E, Najib J, Rapp JH, Williams KJ, Tabas I. Secretory sphingomyelinase, a product of the acid sphingomyelinase gene, can hydrolyze atherogenic lipoproteins at neutral pH. J Biol Chem. . 1998; 273: 2738–2746.
82.
Öörni K, Hakala JK, Annila A, Ala-Korpela M, Kovanen PT. Sphingomyelinase induces aggregation and fusion, but phospholipase A2 only aggregation, of low density lipoprotein particles. J Biol Chem. . 1998; 273: 29127–29134.
83.
Hakala JK, Öörni K, Ala-Korpela M, Kovanen PT. Lipolytic modification of LDL by phospholipase A2 induces particle aggregation in the absence and fusion in the presence of heparin. Arterioscler Thromb Vasc Biol. . 1999; 19: 1276–1283.
84. Iozzo RV. Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem. . 1998; 67: 609–652.[Medline] [Order article via Infotrieve]
85. Tjoelker LW, Stafforini DM. Platelet-activating factor acetylhydrolases in health and disease. Biochim Biophys Acta. . 2000; 1488: 102–123.[Medline] [Order article via Infotrieve]
86. Leach CA, Hickey DMB, Ife RJ, Macphee CH, Smith SA, Tew DG. Lipoprotein-associated PLA 2 inhibition: a novel, non-lipid lowering strategy for atherosclerosis therapy. Farmaco. . 2001; 56: 45–50.[Medline] [Order article via Infotrieve]
87.
Tew DG, Southan C, Rice SQJ, Lawrence MP, Haodong L, Boyd HF, Moores K, Gloger IS, Macphee CH. Purification, properties, sequencing and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins. Arterioscler Thromb Vasc Biol. . 1996; 16: 591–599.
88.
Häkkinen T, Luoma JS, Hiltunen MO, Macphee CH, Millinser KJ, Patel L, Rice SQ, Tew DG, Karkola K, Ylä-Herttuala S. Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions. Arterioscler Thromb Vasc Biol. . 1999; 19: 2909–2917.
89. Cho W. Structure, function, and regulation of group V phospholipase A2. Biochim Biophys Acta. . 2000; 1488: 48–58.[Medline] [Order article via Infotrieve]
90.
Hanasaki K, Ono T, Saiga A, Morioka Y, Ikeda M, Kawamoto K, Higashino K-i, Nakano K, Yamada K, Ishizaki J. Purified group X secretory phospholipase A2 induced prominent release of arachidonic acid from human myeloid leukemia cells. J Biol Chem. . 1999; 274: 34203–34211.
91.
Reddy ST, Winstead MV, Tischfield JA, Herschman HR. Analysis of the secretory phospholipase A2 that mediates prostaglandin production in mast cells. J Biol Chem. . 1997; 272: 13591–13596.
92.
Ho IC, Arm JP, Bingham CO, Choi A, Austen KF, Glimcher LH. A novel group of phospholipase A2s preferentially expressed in type 2 helper T cells. J Biol Chem. . 2001; 276: 18321–18326.
93.
Bezzine S, Koduri RS, Valentin E, Murakami M, Kudo I, Ghomashchi F, Sadilek M, Lambeau G, Gelb MH. Exogenously added human group X secreted phospholipase A2 but not the group IB, IIA, and V enzymes efficiently release arachidonic acid from adherent mammalian cells. J Biol Chem. . 2000; 275: 3179–3191.
94. Jaye M, Lynch KJ, Krawiec J, Marchadier D, Maugeais C, Doan K, South V, Amin D, Perrone M, Rader DJ. A novel endothelial-derived lipase that modulates HDL metabolism. Nat Genet. . 1999; 21: 424–428.[Medline] [Order article via Infotrieve]
95.
Hirata K-i, Dichek HL, Cioffi JA, Choi SY, Leeper NJ, Quintana L, Kronmal GS, Cooper AD, Quertermouse T. Cloning of a unique lipase from endothelial cells extends the lipase gene family. J Biol Chem. . 1999; 274: 14170–14175.
96. Hirata K-i, Ishida T, Matsushita H. Regulated expression of endothelial cell-derived lipase. Biochem Biophys Res Commun. . 2000; 272: 90–93.[Medline] [Order article via Infotrieve]
97. Rader DJ, Jaye M. Endothelial lipase: a new member of the triglyceride lipase gene family. Curr Opin Lipidol. . 2000; 11: 141–147.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  B. Boyanovsky, M. Zack, K. Forrest, and N. R. Webb The Capacity of Group V sPLA2 to Increase Atherogenicity of ApoE-/- and LDLR-/- Mouse LDL In Vitro Predicts its Atherogenic Role In Vivo Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 532 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nijstad, H. Wiersma, T. Gautier, M. van der Giet, C. Maugeais, and U. J. F. Tietge Scavenger Receptor BI-mediated Selective Uptake Is Required for the Remodeling of High Density Lipoprotein by Endothelial Lipase J. Biol. Chem., March 6, 2009; 284(10): 6093 - 6100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sato, R. Kato, Y. Isogai, G.-i. Saka, M. Ohtsuki, Y. Taketomi, K. Yamamoto, K. Tsutsumi, J. Yamada, S. Masuda, et al. Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis J. Biol. Chem., November 28, 2008; 283(48): 33483 - 33497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. J. F. Tietge, N. Nijstad, R. Havinga, J. F. W. Baller, F. H. van der Sluijs, V. W. Bloks, T. Gautier, and F. Kuipers Secretory phospholipase A2 increases SR-BI-mediated selective uptake from HDL but not biliary cholesterol secretion J. Lipid Res., March 1, 2008; 49(3): 563 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N Mazerik, T. Hagele, S. Sherwani, V. Ciapala, S. Butler, M L. Kuppusamy, M. Hunter, P. Kuppusamy, C. B Marsh, and N. L. Parinandi Phospholipase A2 Activation Regulates Cytotoxicity of Methylmercury in Vascular Endothelial Cells International Journal of Toxicology, November 1, 2007; 26(6): 553 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. T.E. Wootton, N. L. Arora, F. Drenos, S. R. Thompson, J. A. Cooper, J. W. Stephens, S. J. Hurel, E. Hurt-Camejo, O. Wiklund, S. E. Humphries, et al. Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong association with LDL and oxLDL levels, suggesting functional distinction from sPLA2-IIA: results from the UDACS study Hum. Mol. Genet., June 15, 2007; 16(12): 1437 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Mallat, J. Benessiano, T. Simon, S. Ederhy, C. Sebella-Arguelles, A. Cohen, V. Huart, N. J. Wareham, R. Luben, K.-T. Khaw, et al. Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and Women: The EPIC-NORFOLK Study Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1177 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Oorni and P. T. Kovanen PLA2-V: A Real Player in Atherogenesis Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 445 - 447. [Full Text] [PDF]
|
|
|
|
|
|
W. Koenig and N. Khuseyinova Biomarkers of Atherosclerotic Plaque Instability and Rupture Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 15 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-A. Karabina, I. Brocheriou, G. Le Naour, M. Agrapart, H. Durand, M. Gelb, G. Lambeau, and E. Ninio Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function FASEB J, December 1, 2006; 20(14): 2547 - 2549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ohtsuki, Y. Taketomi, S. Arata, S. Masuda, Y. Ishikawa, T. Ishii, Y. Takanezawa, J. Aoki, H. Arai, K. Yamamoto, et al. Transgenic Expression of Group V, but Not Group X, Secreted Phospholipase A2 in Mice Leads to Neonatal Lethality because of Lung Dysfunction J. Biol. Chem., November 24, 2006; 281(47): 36420 - 36433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rosengren, H. Peilot, M. Umaerus, A.-C. Jonsson-Rylander, L. Mattsson-Hulten, C. Hallberg, P. Cronet, M. Rodriguez-Lee, and E. Hurt-Camejo Secretory Phospholipase A2 Group V: Lesion Distribution, Activation by Arterial Proteoglycans, and Induction in Aorta by a Western Diet Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1579 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Corsetti, D. L. Rainwater, A. J. Moss, W. Zareba, and C. E. Sparks High Lipoprotein-Associated Phospholipase A2 Is a Risk Factor for Recurrent Coronary Events in Postinfarction Patients Clin. Chem., July 1, 2006; 52(7): 1331 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T.E. Wootton, F. Drenos, J. A. Cooper, S. R. Thompson, J. W. Stephens, E. Hurt-Camejo, O. Wiklund, S. E. Humphries, and P. J. Talmud Tagging-SNP haplotype analysis of the secretory PLA2IIa gene PLA2G2A shows strong association with serum levels of sPLA2IIa: results from the UDACS study Hum. Mol. Genet., January 15, 2006; 15(2): 355 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez-Lee, G. Ostergren-Lunden, B. Wallin, J. Moses, G. Bondjers, and G. Camejo Fatty Acids Cause Alterations of Human Arterial Smooth Muscle Cell Proteoglycans That Increase the Affinity for Low-Density Lipoprotein Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 130 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. J. F. Tietge, D. Pratico, T. Ding, C. D. Funk, R. B. Hildebrand, T. Van Berkel, and M. Van Eck Macrophage-specific expression of group IIA sPLA2 results in accelerated atherogenesis by increasing oxidative stress J. Lipid Res., August 1, 2005; 46(8): 1604 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Williams and I. Tabas Lipoprotein Retention--and Clues for Atheroma Regression Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1536 - 1540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jaulmes, B. Janvier, M. Andreani, and M. Raymondjean Autocrine and Paracrine Transcriptional Regulation of Type IIA Secretory Phospholipase A2 Gene in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1161 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Boekholdt, T. T. Keller, N. J. Wareham, R. Luben, S. A. Bingham, N. E. Day, M. S. Sandhu, J. W. Jukema, J. J.P. Kastelein, C. E. Hack, et al. Serum Levels of Type II Secretory Phospholipase A2 and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women: The EPIC-Norfolk Prospective Population Study Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 839 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chait, C. Y. Han, J. F. Oram, and J. W. Heinecke Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? J. Lipid Res., March 1, 2005; 46(3): 389 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-A. Choi, H.-K. Lim, J.-R. Kim, C.-H. Lee, Y.-J. Kim, S.-S. Kang, and S.-H. Baek Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway J. Biol. Chem., August 27, 2004; 279(35): 36579 - 36585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Oorni, M. Sneck, D. Bromme, M. O. Pentikainen, K. A. Lindstedt, M. Mayranpaa, H. Aitio, and P. T. Kovanen Cysteine Protease Cathepsin F Is Expressed in Human Atherosclerotic Lesions, Is Secreted by Cultured Macrophages, and Modifies Low Density Lipoprotein Particles in Vitro J. Biol. Chem., August 13, 2004; 279(33): 34776 - 34784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Gimenez, Y.-Z. Wu, M. Paya, C. Delclaux, L. Touqui, and P. L. Goossens High Bactericidal Efficiency of Type IIA Phospholipase A2 against Bacillus anthracis and Inhibition of Its Secretion by the Lethal Toxin J. Immunol., July 1, 2004; 173(1): 521 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Wight and M. J. Merrilees Proteoglycans in Atherosclerosis and Restenosis: Key Roles for Versican Circ. Res., May 14, 2004; 94(9): 1158 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Wooton-Kee, B. B. Boyanovsky, M. S. Nasser, W. J.S. de Villiers, and N. R. Webb Group V sPLA2 Hydrolysis of Low-Density Lipoprotein Results in Spontaneous Particle Aggregation and Promotes Macrophage Foam Cell Formation Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 762 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Akiba, Y. Yoneda, S. Ohno, M. Nemoto, and T. Sato Oxidized LDL activates phospholipase A2 to supply fatty acids required for cholesterol esterification J. Lipid Res., September 1, 2003; 44(9): 1676 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Camejo Hydrolytic Enzymes Released From Resident Macrophages and Located in the Intima Extracellular Matrix as Agents That Modify Retained Apolipoprotein B Lipoproteins Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1312 - 1313. [Full Text] [PDF]
|
|
|
|
|
|
H. F. Hoff, J. O'Neil, Z. Wu, G. Hoppe, and R. L. Salomon Phospholipid Hydroxyalkenals: Biological and Chemical Properties of Specific Oxidized Lipids Present in Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 275 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Fuentes, M. Hernandez, F. J. Fernandez-Aviles, M. S. Crespo, and M. L. Nieto Cooperation Between Secretory Phospholipase A2 and TNF-Receptor Superfamily Signaling: Implications for the Inflammatory Response in Atherogenesis Circ. Res., October 18, 2002; 91(8): 681 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Dixon, S. Shen, J. P. Vuchetich, E. Wysocka, G. Y. Sun, and M. Sturek Increased atherosclerosis in diabetic dyslipidemic swine: protection by atorvastatin involves decreased VLDL triglycerides but minimal effects on the lipoprotein profile J. Lipid Res., October 1, 2002; 43(10): 1618 - 1629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. X. Rong, J. W. Berman, M. B. Taubman, and E. A. Fisher Lysophosphatidylcholine Stimulates Monocyte Chemoattractant Protein-1 Gene Expression in Rat Aortic Smooth Muscle Cells Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1617 - 1623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hanasaki, K. Yamada, S. Yamamoto, Y. Ishimoto, A. Saiga, T. Ono, M. Ikeda, M. Notoya, S. Kamitani, and H. Arita Potent Modification of Low Density Lipoprotein by Group X Secretory Phospholipase A2 Is Linked to Macrophage Foam Cell Formation J. Biol. Chem., August 2, 2002; 277(32): 29116 - 29124. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||