© 2000 American Heart Association, Inc.
MiniReview |
The Insulin-Like Growth Factor Axis
A Review of Atherosclerosis and Restenosis
From the Division of Cardiovascular Diseases (A.B.-G., R.S.S.) and Endocrine Research Unit (C.A.C.), Mayo Clinic and Foundation, Rochester, Minn.
Correspondence to Robert S. Schwartz, MD, Department of Cardiovascular Diseases, Mayo Clinic, 200 First St, SW, Rochester, MN 55905. E-mail schwartzr{at}mayo.edu
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Abstract |
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Abstract—Insulin-like growth factors I and II (IGF-I and -II) and their regulatory proteins are secreted by cells of the cardiovascular system. They are growth promoters for arterial cells and mediators of cardiovascular disease. IGFs are bound to IGF binding proteins (IGFBPs), which modulate IGF ligand-receptor interaction and consequently to IGF action. IGFBPs are in turn posttranslationally modulated by specific proteases. This dynamic balance (IGFs, IGFBPs, and IGFBP proteases) constitutes the IGF axis and ultimately determines the extent of IGF-dependent cellular effects. Dysregulated actions of this axis influence coronary atherosclerosis through effects on vascular smooth muscle cell growth, migration, and extracellular matrix synthesis in the atherosclerotic plaque. IGF-I promotes macrophage chemotaxis, excess LDL cholesterol uptake, and release of proinflammatory cytokines. Endothelial cells also receive the effects of IGFs stimulating their migration and organization forming capillary networks. Neointimal hyperplasia of restenosis after coronary artery injury is also modulated by the IGF axis. IGFs stimulate vascular smooth muscle cell proliferation and migration to form the neointima and upregulate tropoelastin synthesis after disruption of the elastic layer. Understanding IGF axis regulation establishes a scientific basis for strategies directed to limit or reverse plaque growth and vulnerability in atherosclerosis and in the neointimal hyperplasia of restenosis.
Key Words: insulin-like growth factor • atherosclerosis • restenosis
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Introduction |
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Insulin-like growth factors I and II (IGF-I and -II) are regular constituents of human blood plasma. Over the past decade, the functions of circulating IGFs have become more clear, but the actions of locally produced IGFs are still ill defined. Accumulating evidence now indicates that IGFs and their regulatory proteins, secreted by cells of the cardiovascular system, are growth promoters for arterial cells and mediators of cardiovascular diseases.1 2 3 4 5 Dysregulated actions of these factors contribute to coronary atherosclerosis and restenosis. This article first reviews the basic physiology of the IGF axis and then discusses specific autocrine and paracrine actions of IGFs in atherosclerotic plaque progression and the neointimal hyperplasia of restenosis.
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The IGF Axis |
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IGF-I and IGF-II are single-chain polypeptides (70 and 67 amino acids, respectively) that share homology with each other and with proinsulin.6 Systemic IGF-I and IGF-II levels are determined mainly by production in the liver. However, many cells of the body synthesize these growth factors.6 The IGFs have a broad range of physiological actions starting with early embryonic development and extending throughout life. Metabolic functions, particularly glucose metabolism, constitute an important aspect of IGF-I and -II activities.7 The IGFs also induce differentiated functions of cells stimulating amino acid uptake and protein synthesis,8 and promoting migration.9 Another prominent aspect of IGF-I is regulation of cell cycle progression and mitogenesis.10 11 IGFs may also function as survival factors by decreasing apoptosis in various cells.12
The actions of IGFs are mediated by specific membrane
receptors.13 Type I IGF receptor, homologous to the
insulin receptor, contains 2 
and 2 ß subunits and has tyrosine
kinase activity responsible for IGF-I and IGF-II intracellular
signaling (Figure 1C
). Type II IGF
receptor, identical to mannose-6-phosphate receptor, has an uncertain
role in growth factor signaling.14 Recently, IGF-II also
showed mitogenic effects through a high-affinity
interaction with isoform A of the insulin receptor.15
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The ultimate cell response to IGFs depends on the context of IGF
binding proteins (IGFBPs). Six different IGFBPs have been
identified.16 The IGFBP that carries most circulating IGF
(>90% in adult serum) is IGFBP-3, existing predominantly as a 150-kDa
"ternary" complex consisting of an additional protein termed the
acid-labile subunit.17 This complex restricts the
extravascular transit and is a circulating store for IGFs. At the
cellular level, IGFBPs form a binary complex with IGFs and critically
modulate local IGF actions18 (Figure 1A
). A further
refinement of this axis is recent evidence that IGFBPs undergo
posttranslational modification. Proteolytic activity of the IGFBP
proteases results in modulation of IGFBP affinity for IGFs or complete
destruction of IGF binding potential.19 IGFBP proteases
regulate IGF half-life and play a critical role in modulating IGF
availability at the cellular level19 20 21 22 (Figure 1B). This dynamic balance (IGFs, IGFBPs, and IGFBP proteases)
constitutes the IGF axis and ultimately determines the extent of
IGF-dependent cellular effects.
The next sections outline the relation between the IGF axis and 2 important vascular pathologies, atherosclerosis and restenosis.
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Atherosclerosis |
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Atherosclerotic plaque develops over several decades and involves inflammatory cell infiltration, smooth muscle cell proliferation, accumulation of extracellular matrix, fibrous cap formation, and angiogenesis. Among the various growth factors involved in atherosclerotic plaque development, IGFs play a relevant role (Figure 2
). The different cell types of
atherosclerosis secrete IGFs, and type I IGF receptors
are present on smooth muscle cells,23 inflammatory
cells,24 and arterial
endothelial cells25 within the
atherosclerotic lesion.
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Activation of Vascular Smooth Muscle Cells (VSMCs)
VSMC dysregulation at atherosclerotic sites is associated with a
shift from the so-called contractile-to-synthetic phenotype and
displays many features of growth factor activation. Several in vitro
studies of both animal26 27 and human VSMCs28
show that IGF-I induces cell cycle changes resulting in VSMC
proliferation and migration.11 IGF-I and
platelet-derived growth factor (PDGF) act synergistically to
stimulate VSMC proliferation.29 IGF growth-promoting
effects are also interactive with the effects of
angiotensin II and basic fibroblast growth
factor.30 31
Studies of ischemic patients reinforce the IGF effects seen in vitro. Coronary atherectomy specimens show markedly increased IGF-I, type I IGF receptor, and IGFBPs 1 to 5 in VSMCs.2 Intense localization of these proteins occurs primarily in the cytoplasm of VSMCs exhibiting the synthetic phenotype. Pfeifle and Ditschuneit23 showed that type I IGF receptor expression varies with cellular growth status. These observations suggest that IGF axis protein synthesis and secretion depend on the phenotypic state of plaque-derived VSMCs.
A recent study of severely atherosclerotic patients showed higher IGF-I mRNA expression in regions containing densely packed VSMCs within the active plaque, compared with lower levels found in stable plaques.3 Morbidity and mortality of atherosclerotic patients is significantly reduced with the use of statins.32 33 The statins inhibit 3-hydroxy-3-methyl-glutharyl–coenzyme A reductase and thus reduce endogenous cholesterol synthesis. Some statin effects also are mediated by IGF-I, because lovastatin efficiently blocks intracellular signaling pathways activated by IGF-I and limit VSMC proliferation.34
Migration of VSMCs from the media is a major pathologic vascular
response leading to the development and progression of the lesions of
atherosclerosis. IGFs are potent stimuli of VSMC
migration,9 35 and the effect appears to be mediated
through type I IGF receptor.35 Interestingly, one of the
IGFBPs, IGFBP-1, stimulates migration independent of IGF-I via the
5ß1
integrin.36
VSMC apoptosis occurs in the evolutionary process of atherosclerotic plaques.37 This programmed cell death can be suppressed by high IGF-I and PDGF concentrations, a finding consistent with recent studies of IGF-I and PDGF as potent survival factors for rat VSMCs.38 Likewise, constitutive overexpression of IGF-I prevents cell death of viable myocardium after infarction, limiting ventricular dilation, myocardial loading, and cardiac hypertrophy.39 Current information on IGF cardioprotective activity can be found in recent reviews.40 41 Yet the IGF-I requirement for cell survival shown both in vitro and in vivo is uncertain in the vessel wall in the presence of IGFBP and IGFBP proteases.
Little is known about IGFBPs and proteases in
atherosclerosis. IGFBP-2 and -4 are the more prevalent
binding proteins secreted by VSMCs.42 43 44 IGFBP-2
stimulates IGF-dependent mitosis in porcine VSMCs in the presence of
platelet-poor plasma and inhibits DNA synthesis in serum-free
medium, suggesting that the presence of a factor in plasma is required
for IGFBP-2 to potentiate IGF effects.45 Interestingly,
IGFBP-2 inhibits IGF-stimulated VSMC migration by preventing type I IGF
receptor interaction.35 IGFBP-4 consistently
inhibits IGF-mediated actions in all cell types
studied.46 47 Specific proteases have been identified in
VSMCs for these binding proteins,44 which modify IGFBPs,
and hence, IGF biological activity (Figure 1). We recently
isolated a novel IGF-dependent IGFBP-4–specific protease and
identified it as pregnancy-associated plasma protein-A
(PAPP-A),48 a member of the metzincin family of
metalloproteinases.49 By cleaving IGFBP-4 and releasing
free IGF-I, PAPP-A appears to modulate growth in local proliferative
responses.47 50 51
Independent of its growth-promoting properties, IGF-I induces coronary vasorelaxation acting primarily on VSMCs. Sowers52 found increased VSMC production of inducible NO under IGF-I stimulation, whereas others suggest that coronary vasorelaxation is due to activation of the potassium channels independently of NO.53 Whichever pathway prevails, IGF-I maintains coronary epicardial vasomotor tone in pathophysiologic states.
Macrophage Activation
Macrophage accumulation is an early event in
atherosclerosis. Macrophages are crucial in
inflammatory processes associated with tissue injury through the
ability to induce phagocytosis and to release proteases and
cytokines.54
High-affinity type I IGF receptors on the macrophage surface
allow IGFs to modulate macrophage concentrations at injury
sites.24 Human macrophages also synthesize and
secrete IGF-I55 and some of the binding
proteins.56 IGF-I secreted within the atherosclerotic
lesion is important for monocyte chemotaxis, activation, and
cytokine release (ie, tumor necrosis
factor-).57 It is likely that
macrophage-derived IGF enhances cellular LDL uptake and
degradation and also the macrophage cholesterol
esterification rate.24
Angiogenesis
Normal coronary arteries have no vessels within the inner
media or intima. Angiogenesis occurs as part of the normal
wound-healing process and also in
atherosclerosis.58 59 Many growth factors
regulate angiogenesis, stimulating migration, proliferation,
proteolytic activity, and organizational behavior of
endothelial cells.60 61 These angiogenic
factors include basic fibroblast growth factor, vascular
endothelial growth factor, transforming growth
factor-ß, and IGF-I.62 63
Endothelial cells from both capillaries and arteries possess specific receptors for IGF-I25 and secrete IGF-I and IGFBPs (specifically IGFBP-2, -3, and -4).1 Locally synthesized IGF-I at sites of lesion formation stimulates vascular injury repair promoting endothelial cell migration. IGF-I has a chemotactic action on vascular endothelial cells64 and induces endothelial tube–forming activity in vitro.62 These endothelial conduits receive the influence of other factors in the process of maturation to become fully organized capillaries.
Inflammatory angiogenesis occurs in atherogenesis and involves both endothelial cells and macrophages. Animal studies of inflammation-linked angiogenesis produced after microembolization of a coronary artery showed alterations in gene expression of IGF-I and the binding proteins 3, 5, and 6 in macrophages.65
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Restenosis |
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Coronary restenosis remains a major clinical problem after all percutaneous revascularization procedures. Morphology in the pig stent model66 and after human coronary stenting demonstrates early thrombus formation and inflammation followed by neointimal growth.67 Smooth muscle cell accumulation is key to neointimal formation after angioplasty. Several studies indicate that IGF-I is involved in local cellular events leading to restenosis after coronary angioplasty.5 68 IGF-I immunoreactivity is present in medial VSMCs and in the neointima after arterial injury in the rat.68 IGF-I paracrine effects in vascular repair are also evident by aortic IGF-I gene induction associated with receptor downregulation after balloon injury.69 RT-PCR analysis revealed increased mRNA levels of IGF-I and IGFBP-1 to -5 in human restenotic lesions,2 reinforcing the autocrine-paracrine synthesis of the IGF axis proteins within the vessel wall after injury.
In the early stages of restenosis, VSMC IGF-I from human restenotic specimens is far higher than in normal coronary VSMCs.28 However, restenotic tissue obtained several months after the intervention showed no IGF-I mRNA expression.3 The predominant IGF-I production and action in arterial media suggests that IGF-I has a growth-promoting effect on VSMCs after balloon injury. In fact, transgenic mice with IGF-I overexpression show vascular smooth muscle hyperplasia.70 Furthermore, mice with paracrine overproduction of IGFBP-4 developed smooth muscle hypoplasia,71 supporting the concept that IGFBP-4 inhibits IGF-I action. IGFBP-4 proteolysis by highly specific IGFBP-4 proteases remains an important issue, as tissue bioactive IGF-I rises after vascular injury. We recently found that VSMC injury increases the expression and proteolytic activity of PAPP-A (IGFBP-4 protease), which in turn releases free IGF-I and appears to be intimately involved in the development of neointimal hyperplasia (A. Bayes-Genis et al, unpublished data, 1999).
IGFs also serve beneficial effects at the vessel wall after injury. A number of studies show that VSMC elastogenesis is increased by IGF-I both in vitro72 73 and in vivo.74 Elastin expression is controlled at the transcriptional level by IGF-I and at the posttranscriptional level by transforming growth factor-ß.75 Foster et al72 found that tropoelastin comprised >50% of total protein synthesis by IGF-I in aortic tissues. As the media is stretched and damaged by balloon inflation, it is reasonable to assume that local IGF-I production may play a role in regenerating the elastic layer.
IGF-I inhibitors such as the somatostatin analogues octreotide and angiopeptin show significant inhibition of VSMC proliferation and neointimal formation in animal studies.76 77 78 79 However, placebo-controlled clinical trials are equivocal for angiopeptin80 81 82 and indicate no benefit for octreotide.83 Thus, it remains to be demonstrated that somatostatin analogues are an effective anti-restenosis strategy.
In conclusion, this review of experimental and clinical studies supports the importance of the IGF axis in atherosclerosis and restenosis. The IGF axis is complex. Many possible interactions of its components account for functional diversity, the extent of which is only now beginning to be understood. Alterations in the balance of the components of the IGF axis in the vessel wall influence the cell growth, survival, migration, and extracellular matrix synthesis that modulate atherosclerotic plaque progression and neointimal formation of restenosis. A better understanding of IGF axis dynamics could identify new targets to limit or prevent these vascular pathologies.
Received August 2, 1999; accepted October 27, 1999.
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References |
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|---|
1. Delafontaine P. Insulin-like growth factor I and its binding proteins in the cardiovascular system. Cardiovasc Res. 1995;30:825–834.[Medline] [Order article via Infotrieve]
2. Grant MB, Wargovich TJ, Ellis EA, Tarnuzzer R, Caballero S, Estes K, Rossig M, Spoerri PE, Pepine C. Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, -2, -3, -4 and -5 in human atherectomy specimens. Regul Pept. 1996;67:137–144.[Medline] [Order article via Infotrieve]
3. Wilson VJ, Ward JPT, Burnand KG, Thomas CR. Upregulation of IGF-I and collagen I mRNA in human atherosclerotic tissue is not accompanied by changes in type 1 IGF receptor or collagen III mRNA: an in situ hybridization study. Coron Artery Dis. 1996;7:569–572.[Medline] [Order article via Infotrieve]
4. Fernas GAA, Morani AS, Anggard EE. The insulin-like growth factors: their putative role in atherogenesis. Artery. 1991;18:197–225.[Medline] [Order article via Infotrieve]
5. Cercek B, Sharifi B, Barath P, Bailey L, Forrester JS. Growth factors in pathogenesis of coronary arterial restenosis. Am J Cardiol. 1991;68:24C–33C.[Medline] [Order article via Infotrieve]
6.
Daughaday WH, Rotwein P. Insulin-like growth factors I
and II: peptide, messenger ribonucleic acid and gene structures, serum,
and tissue concentrations. Endocr Rev. 1989;10:68–91.
7. Jacob R, Barrett E, Plewe G, Fagin KD, Sherwin RJ. Acute effects of insulin-like growth factor I on glucose and amino acid metabolism in the awake fasted rat. J Clin Invest. 1989;83:1717–1723.
8.
Boulware SD, Tamborlane WV, Matthews LS, Sherwin RS.
Diffuse effects of insulin-like growth factor I on glucose, lipid, and
amino acid metabolism. Am J Physiol. 1992;262:E130–E133.
9. Bornfeldt KE, Rainco EW, Nateano T, Groves LM, Krebs E, Ross R. Insulin-like growth factor I and platelet-derived growth factor-BB directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation. J Clin Invest. 1993;93:1266–1274.
10. Baserga R, Rubin R. Cell cycle and growth control. Crit Rev Eukaryot Gene Expr. 1993;3:47–61.[Medline] [Order article via Infotrieve]
11.
Stiles CD, Capone GT, Scher CD, Antoniades HN, Van Wyk
JJ, Pledger WJ. Dual control of cell growth by somatomedins and
platelet-derived growth factor. Proc Natl Acad Sci
U S A. 1979;76:1279–1283.
12.
Parrizas M, Saltiel AR, LeRoith D. Insulin-like growth
factor I inhibits apoptosis using the phosphatidylinositol-3
kinase and mitogen-activated protein kinase pathways.
J Biol Chem. 1997;272:154–161.
13.
LeRoith D, Werner H, Beitner-Johnson D, Roberts CT.
Molecular and cellular aspects of the insulin-like growth factor I
receptor. Endocr Rev. 1995;16:143–163.
14.
MacDonald RG, Pfeffer SR, Coussens L, Tepper MA,
Blocklebank CM, Mole JE, Anderson JK, Chen E, Czech MP, Ullrich A. A
single receptor binds both insulin-like growth factor II and mannose
6-phosphate. Science. 1988;239:1134–1137.
15.
Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R,
Costantino A, Goldfine ID, Belfiore A, Vigneri R. Insulin receptor
isoform A, a newly recognized, high-affinity insulin-like growth factor
II receptor in fetal and cancer cells. Mol Cell Biol. 1999;19:3278–3288.
16. Shimasaki S, Ling N. Identification and molecular characterization of insulin-like growth factor binding protein (IGFBP-1, -2, -3, -4, -5, and -6). Prog Growth Factor Res. 1991;3:243–266.[Medline] [Order article via Infotrieve]
17. Baxter RC. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res. 1994;42:140–144.[Medline] [Order article via Infotrieve]
18. Kelley KM, Oh Y, Gargosky SE, Gucev Z, Matsumoto T, Hwa V, Ng l, Simpson DM. Insulin-like growth factor-binding protein (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol. 1996;28:619–637.[Medline] [Order article via Infotrieve]
19. Conover CA. Posttranslational modification of the IGF binding proteins. In: Contemporary Endocrinology: The IGF System. Totowa, NJ: Humana Press, Inc; 1999:355–376.
20. Blat C, Villaundy J, Binoux M. In vivo proteolysis of serum IGFBP-3 results in increased availability of IGF to target cells. J Clin Invest. 1994;93:2286–2290.
21. Rajah R, Katz L, Nunn S, Solberg P, Beers T, Cohen P. Insulin-like growth factor binding protein (IGFBP) proteases: functional regulators of cell growth. Prog Growth Factor Res. 1995;6:273–284.[Medline] [Order article via Infotrieve]
22. Nam TJ, Busby WM, Clemmons DR. Human fibroblasts secrete a serine protease that cleaves insulin-like growth factor binding protein-5. Endocrinology. 1994;135:1385–1391.[Abstract]
23.
Pfeifle B, Ditschuneit H. Receptors for insulin and
insulin-like growth factor in cultured arterial smooth
muscle cells depend on their growth state. J Endocrinol. 1983;96:251–257.
24.
Hochberg Z, Hertz P, Maor G, Oiknine J, Aviram M.
Growth hormone and insulin-like growth factor I increase
macrophage uptake and degradation of low-density lipoprotein.
Endocrinology. 1992;131:430–435.
25. Bar RS, Boes M. Distinct receptors for IGF-I, IGF-II, and insulin are present on bovine capillary endothelial cells and large vessel endothelial cells. Biochem Biophys Res Commun. 1984;124:203–209.[Medline] [Order article via Infotrieve]
26.
Delafontaine P, Lou H, Alexander RW. Regulation of
insulin-like growth factor I messenger RNA levels in vascular smooth
muscle cells. Hypertension. 1991;18:742–747.
27.
Clemmons DR. Variables controlling the secretion of
a somatomedin-like peptide by cultured porcine smooth muscle cells.
Circ Res. 1985;56:418–426.
28.
Grant MB, Wargovich TJ, Ellis EA, Caballero S, Mansour
M, Pepine CJ. Localization of insulin-like growth factor I and
inhibition of coronary smooth muscle cell growth by
somatostatin analogues in human coronary smooth muscle cells: a
potential treatment for restenosis? Circulation. 1994;89:1511–1517.
29.
Banskota NK, Taub R, Zeller K, King GL. Insulin,
insulin-like growth factor I and platelet-derived growth factor
interact additively in the induction of the protooncogene c-myc and
cellular proliferation in cultured bovine aortic smooth muscle cells.
Mol Endocrinol. 1989;3:1183–1190.
30.
Delafontaine P, Lou H. Angiotensin II
regulates insulin-like growth factor I gene expression in vascular
smooth muscle cells. J Biol Chem. 1993;268:16866–16870.
31. Clemmons DR. Interaction of circulating cell-derived and plasma growth factors in stimulating cultured smooth muscle cell replication. J Cell Physiol. 1984;121:425–430.[Medline] [Order article via Infotrieve]
32.
Pedersen TR, Berg K, Cook TJ, Faergeman O, Haghfelt T,
Kjekshus J, Miettinen T, Musliner TA, Alsson AG, Pyorala K,
Thorgeirsson G, Tobert JA, Wedel H, Wilhelmsen L. Safety and
tolerability of cholesterol lowering with
simvastatin during 5 years in the Scandinavian
Simvastatin Survival Study. Arch Intern Med. 1996;156:2085–2092.
33. Watts GF, Burke V. Lipid-lowering trials in the primary and secondary prevention of coronary heart disease: new evidence, implications and outstanding issues. Curr Opin Lipidol. 1996;7:341–355.[Medline] [Order article via Infotrieve]
34. Martinez-Gonzalez J, Viñals M, Vidal F, Llorente-Cortes V, Badimon L. Mevalonate deprivation impairs IGF-I/insulin signaling in human vascular smooth muscle cells. Atherosclerosis. 1997;135:213–223.[Medline] [Order article via Infotrieve]
35. Gockerman A, Prevette T, Jones JI, Clemmons DR. Insulin-like growth factor (IGF)-binding proteins inhibit the smooth muscle cell migration responses to IGF-I and IGF-II. Endocrinology. 1995;136:4168–4173.[Abstract]
36.
Jones JI, Gockerman A, Busby WH, Wright G, Clemmons DR.
Insulin-like growth factor binding protein 1 stimulates cell migration
and binds to the 5ß1 integrin by means of its Arg-Gly-Asp
sequence. Proc Natl Acad Sci U S A. 1993;90:10553–10557.
37. Bennet MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest. 1995;95:2266–2274.
38.
Bennet MR, Evan GI, Newby AC. Deregulated c-myc
oncogene expression blocks vascular smooth muscle cell inhibition
mediated by heparin, interferon-gamma, mitogen depletion and cyclic
nucleotide analogues and induces apoptotic cell
death. Circ Res. 1994;74:525–536.
39. Li Q, Li B, Wang X, Leri A, Jana K, Liu Y, Kajstura J, Baserga R, Anversa P. Overexpression of insulin-like growth factor I in mice protects from myocyte death after infarction, attenuating dilation, wall stress, and cardiac hypertrophy. J Clin Invest. 1997;100:1991–1999.[Medline] [Order article via Infotrieve]
40.
Anversa P, Kajstura J. Ventricular myocytes
are not terminally differentiated in the adult mammalian heart.
Circ Res. 1998;83:1–14.
41. Bartling B, Holtz J, Darmer D. Contribution of myocyte apoptosis to myocardial infarction. Basic Res Cardiol. 1998;93:71–84.[Medline] [Order article via Infotrieve]
42. Cohick WS, Gockerman A, Clemmons DR. Vascular smooth muscle cells synthesize 2 forms of insulin-like growth factor binding protein (IGFBP) which are regulated differentially by the insulin-like growth factors. J Cell Physiol. 1993;157:52–60.[Medline] [Order article via Infotrieve]
43.
Giannella-Neto D, Kamyar A, Sharifi B, Picola CJ,
Kupfer J, Rosenfeld RG, Forrester JS, Fagin JA. Platelet-derived
growth factor isoforms decrease insulin-like growth factor I gene
expression in rat vascular smooth muscle cells and selectively
stimulate the biosynthesis of insulin-like growth factor binding
protein 4. Circ Res. 1992;71:646–656.
44.
Gockerman A, Clemmons DR. Porcine aortic smooth muscle
cells secrete a serine protease for insulin-like growth factor binding
protein-2. Circ Res. 1995;76:514–521.
45. Bourner MJ, Busby WH, Seigle NR, Krivi GG, McCusker RH, Clemmons DR. Cloning and sequence determination of bovine IGFBP-2: comparison of its structural and functional properties with IGFBP-1. J Cell Biochem. 1992;48:215–226.[Medline] [Order article via Infotrieve]
46.
Cheung PT, Smith EP, Shimasaki S, Ling N, Chernausek
SD. Characterization of an insulin like growth factor binding protein
(IGFBP-4) produced by the B104 rat neuronal cell line, chemical and
biological properties and differential synthesis by sublines.
Endocrinology. 1991;129:1006–1015.
47. Conover CA, Kiefer MC, Zapf J. Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts: insulin-like growth factor dependence and biological studies. J Clin Invest. 1993;91:1129–1137.
48.
Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L,
Gleich GJ, Hays LG, Yates JR III, Conover CA. The insulin-like growth
factor (IGF)-dependent IGF binding protein-4 protease secreted by human
fibroblasts is pregnancy associated plasma protein-A. Proc Natl
Acad Sci U S A. 1999;96:3149–3153.
49. Kristensen T, Oxvig C, Sand O, Moller NP, Sottrup-Jensen L. Amino-acid sequence of human pregnancy associated plasma protein-A derived from cloned cDNA. Biochemistry. 1994;33:1592–1598.[Medline] [Order article via Infotrieve]
50. Irwin JC, Dsupin BA, Giudice LC. Regulation of insulin-like growth factor-binding protein-4 in human endometrial stromal cell cultures: evidence for ligand-induced proteolysis. J Clin Endocrinol Metab. 1995;80:619–626.[Abstract]
51. Conover CA. Insulin-like growth factor binding protein proteolysis in bone cell models. Prog Growth Factor Res. 1995;6:301–309.[Medline] [Order article via Infotrieve]
52.
Sowers JR. Insulin and insulin-like growth factor in
normal and pathological cardiovascular physiology.
Hypertension. 1997;29:691–699.
53.
Hasdai D, Rizza R, Holmes DR Jr, Richardson DM, Cohen
P, Lerman A. Insulin and insulin-like growth factor I cause
coronary vasorelaxation in vitro. Hypertension. 1998;32:228–234.
54.
Noble PW, Lake FR, Henson PM, Riches DW. Hyaluronate
activation of CD44 induces insulin-like growth factor I expression by a
tumor necrosis factor-–dependent mechanism in murine
macrophages. J Clin Invest. 1993;91:2368–2377.
55. Nagaoka I, Trapnell BC, Crystal RG. Regulation of insulin-like growth factor I gene expression in the human macrophage-like cell line U937. J Clin Invest. 1990;85:448–455.
56. Li YM, Arkins S, McCusker RH Jr, Donovan SM, Liu Q, Jayaraman S, Dantzer R, Kelley KW. Macrophages synthesize and secrete a 25-kilodalton protein that binds insulin-like growth factor I. J Immunol. 1996;156:64–72.[Abstract]
57.
Renier G, Clement I, Desfaits AC, Lambert A. Direct
stimulatory effect of insulin-like growth factor I on monocyte and
macrophage tumor necrosis- production.
Endocrinology. 1996;137:4611–4618.[Abstract]
58.
Kwoon HM, Sangiorgi G, Ritman EL, Lerman A, McKenna C,
Virmani R, Edwards WD, Holmes DR, Schwartz RS. Adventitial vasa vasorum
in balloon-injured coronary arteries: visualization and
quantitation by a microscopic three-dimensional computed tomography
technique. J Am Coll Cardiol. 1998;32:2072–2079.
59. Kumamoto M, Nakashima Y, Sueishi K. Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol. 1995;26:450–456.[Medline] [Order article via Infotrieve]
60.
Folkman J, Shing Y. Angiogenesis. J Biol
Chem. 1992;267:10931–10934.
61. Thompson WD, Stirk CM, Melvin WT, Smith EB. Plasmin, fibrin degradation and angiogenesis. Nat Med. 1996;2:493.[Medline] [Order article via Infotrieve]
62. Nicosia RF, Nicosia SV, Smith M. Vascular endothelial growth actor, platelet-derived growth factor, and insulin-like growth factor I promote rat aortic angiogenesis in vitro. Am J Pathol. 1994;145:1023–1029.[Abstract]
63. Grant MB, Names RN, Fitzgerald C, Ellis EA, Caballero S, Chegini N, Guy J. Insulin-like growth factor I as an angiogenic agent: in vivo and in vitro studies: the role of insulin-like growth factors in the nervous system. Ann N Y Acad Sci. 1993;692:230–242.[Medline] [Order article via Infotrieve]
64.
Grant MB, Jordan J, Merimee TJ. Insulin-like
growth factor I modulates endothelial cell chemotaxis.
J Clin Endocrinol Metab. 1987;65:370–371.
65.
Kluge A, Zimmermann R, Weihrauch D, Mohri M, Sack S,
Schaper J, Schaper W. Coordinate expression of the insulin-like growth
factor system after microembolisation in porcine heart.
Cardiovasc Res. 1997;33:324–331.
66.
Schwartz RS, Murphy JG, Edwards WD, Camrud AR, Vliestra
RE, Holmes DR. Restenosis after balloon angioplasty: a
practical proliferative model in porcine coronary arteries.
Circulation. 1990;82:2190–2200.
67. Farb A, Sangiorgi G, Carter AJ, Walley VM, Edwards W, Schwartz RS, Virmani R. Pathology of acute and chronic coronary stenting in humans. Circulation. 1999;99:4–52.
68. Hansson HA, Jennische E, Skottner A. Regenerating endothelial cells express insulin-like growth factor I immunoreactivity after arterial injury. Cell Tissue Res. 1987;250:499–505.[Medline] [Order article via Infotrieve]
69. Khorsandi MJ, Fagin JA, Gianella-Neto D, Forrester JS, Cercek B. Regulation of insulin-like growth factor I and its receptor in rat aorta after balloon denudation: evidence for local bioactivity. J Clin Invest. 1992;90:1926–1931.
70. Wang J, Niu W, Nikiforov Y, Naito S, Chernausek S, Witte D, LeRoith D, Strauch A, Fagin JA. Targeted overexpression of insulin-like growth factor I evokes distinct patterns of organ remodeling in smooth muscle cell tissue beds of transgenic mice. J Clin Invest. 1997;100:1425–1439.[Medline] [Order article via Infotrieve]
71.
Wang J, Niu W, Witte DP, Chernausek SD, Nikiforov YE,
Clemens TL, Sharifi B, Strauch AR, Fagin JA. Overexpression of
insulin-like growth factor binding protein-4 (IGFBP-4) in smooth muscle
cells of transgenic mice through a smooth muscle -actin-IGFBP-4
fusion gene induces smooth muscle hypoplasia. Endocrinology. 1998;139:2605–2614.
72. Foster JA, Rich CB, Horrikan SK. Tropoelastin synthesis in fetal bovine tissues. Collagen Rel Res. 1986;6:387–396.
73.
Rich CB, Ewton DZ, Martin BM, Florini JR, Bashir M,
Rosenbloom J, Foster JA. Insulin-like growth factor I regulation of
elastogenesis: comparison of aortic and lung cells. Am J
Physiol. 1992;263:L276–L282.
74. Foster JA, Rich CB, Miller ML, Benedict MR, Richman RA, Florini JR. Effect of age and insulin-like growth factor I administration on elastin gene expression in rat aorta. J Gerontol. 1990;45:113–118.
75. Debelle L, Tamburro AM. Elastin, molecular description and function. Int J Biochem Cell Biol. 1999;31:261–272.[Medline] [Order article via Infotrieve]
76. Lundergan CF, Foegh ML, Vargas R, Eufemio M, Bormes GW, Kot PA, Ramwell PW. Inhibition of myointimal proliferation of the rat carotid artery by the peptides, angiopeptin and BIM 23034. Atherosclerosis. 1989;80:49–55.[Medline] [Order article via Infotrieve]
77.
Santoian ED, Schneider J, Gravanis M, Foegh M, Tarazona
N, Cipolla G, King SB III. Angiopeptin inhibits intimal hyperplasia
after angioplasty in porcine coronary arteries.
Circulation. 1993;88:11–14.
78.
Bauters C, VanBelle E, Wernert N, Delcayre C,
Thomas F, Dupuis B, Lablanche JM, Bertrand ME, Swynghedauw B.
Angiopeptin inhibits oncogene induction in rabbit aorta after balloon
denudation. Circulation. 1994;89:2327–2331.
79.
Serri O, Brazeau P, Posner B. Octreotide inhibits
insulin-like growth factor I hepatic gene expression in the
hypophysectomized rat: evidence for a direct and indirect mechanism of
action. Endocrinology. 1992;130:1816–1821.
80. Kent KM, Williams DO, Cassagneau D. Double blind, controlled trial of the effect of angiopeptin on coronary restenosis following balloon angioplasty. Circulation. 1993;88 (suppl I):I-506. Abstract.
81. Eriksen UH, Amtorp O, Bagger JP, Emanuelsson H, Foegh M, Henningsen P, Saunamaki K, Schaeffer M, Thayssen P, Orskov H. Randomized double-blind Scandinavian trial of angiopeptin versus placebo for the prevention of clinical events and restenosis after coronary balloon angioplasty. Am Heart J. 1993;130:1–8.
82.
Emanuelsson H, Beatt KJ, Bagger JP, Balcon R,
Heikkilä J, Piessens J, Schaeffer M, Suryapranata H, Foegh ML.
Long-term effects of angiopeptin treatment in coronary
angioplasty: reduction of clinical events but not angiographic
restenosis. Circulation. 1995;91:1689–1696.
83.
VonEssen R, Ostermaier R, Grube E, Maurer W, Tebbe U,
Erbel R, Roth M, Oel W, Brom J, Weidinger G. Effects of octreotide on
restenosis after coronary angioplasty: results of the
VERAS study. Circulation. 1997;96:1482–1487.
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 D. L. Hunton, W. G. Barnes, J. Kim, X.-R. Ren, J. D. Violin, E. Reiter, G. Milligan, D. D. Patel, and R. J. Lefkowitz {beta}-Arrestin 2-Dependent Angiotensin II Type 1A Receptor-Mediated Pathway of Chemotaxis Mol. Pharmacol., April 1, 2005; 67(4): 1229 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 J. T. Wu and L. L. Wu Association of Soluble Markers with Various Stages and Major Events of Atherosclerosis Ann. Clin. Lab. Sci., January 1, 2005; 35(3): 240 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q.-P. Qin, S. Kokkala, J. Lund, N. Tamm, L.-M. Voipio-Pulkki, and K. Pettersson Molecular Distinction of Circulating Pregnancy-Associated Plasma Protein A in Myocardial Infarction and Pregnancy Clin. Chem., January 1, 2005; 51(1): 75 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 L. A. Colangelo, K. Liu, and S. M. Gapstur Insulin-like Growth Factor-1, Insulin-like Growth Factor Binding Protein-3, and Cardiovascular Disease Risk Factors in Young Black Men and White Men: The CARDIA Male Hormone Study Am. J. Epidemiol., October 15, 2004; 160(8): 750 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Conti, C. Carrozza, E. Capoluongo, M. Volpe, F. Crea, C. Zuppi, and F. Andreotti Insulin-Like Growth Factor-1 as a Vascular Protective Factor Circulation, October 12, 2004; 110(15): 2260 - 2265. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
B Gonzalez-Timon, M Gonzalez-Munoz, C Zaragoza, S Lamas, and E.M Melian Native and oxidized low density lipoproteins oppositely modulate the effects of insulin-like growth factor I on VSMC Cardiovasc Res, February 1, 2004; 61(2): 247 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 A. Girnita, L. Girnita, F. d. Prete, A. Bartolazzi, O. Larsson, and M. Axelson Cyclolignans as Inhibitors of the Insulin-Like Growth Factor-1 Receptor and Malignant Cell Growth Cancer Res., January 1, 2004; 64(1): 236 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ruiz-Torres, R. Lozano, J. Melon, and R. Carraro Age-Dependent Decline of In Vitro Migration (Basal and Stimulated by IGF-1 or Insulin) of Human Vascular Smooth Muscle Cells J Gerontol A Biol Sci Med Sci, December 1, 2003; 58(12): B1074 - B1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
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T. Sasaoka, K. Kikuchi, T. Wada, A. Sato, H. Hori, S. Murakami, K. Fukui, H. Ishihara, R. Aota, I. Kimura, et al. Dual Role of Src Homology Domain 2-Containing Inositol Phosphatase 2 in the Regulation of Platelet-Derived Growth Factor and Insulin-Like Growth Factor I Signaling in Rat Vascular Smooth Muscle Cells Endocrinology, September 1, 2003; 144(9): 4204 - 4214. [Abstract] [Full Text] [PDF]
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 A. La Batide-Alanore, D.-A. Tregouet, C. Sass, G. Siest, S. Visvikis, and L. Tiret Family study of the relationship between height and cardiovascular risk factors in the STANISLAS cohort Int. J. Epidemiol., August 1, 2003; 32(4): 607 - 614. [Abstract] [Full Text] [PDF]
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 A.F.C. Schut, J.A.M.J.L. Janssen, J. Deinum, J.M. Vergeer, A. Hofman, S.W.J. Lamberts, B.A. Oostra, H.A.P. Pols, J.C.M. Witteman, and C.M. van Duijn Polymorphism in the Promoter Region of the Insulin-like Growth Factor I Gene Is Related to Carotid Intima-Media Thickness and Aortic Pulse Wave Velocity in Subjects With Hypertension Stroke, July 1, 2003; 34(7): 1623 - 1627. [Abstract] [Full Text] [PDF]
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T. B. Twickler, M. J. M. Cramer, G. M. Dallinga-Thie, M. J. Chapman, D. W. Erkelens, and H. P. F. Koppeschaar Adult-Onset Growth Hormone Deficiency: Relation of Postprandial Dyslipidemia to Premature Atherosclerosis J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2479 - 2488. [Full Text] [PDF]
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R. Napoli, V. Guardasole, V. Angelini, F. D'Amico, E. Zarra, M. Matarazzo, and L. Sacca Acute Effects of Growth Hormone on Vascular Function in Human Subjects J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2817 - 2820. [Abstract] [Full Text] [PDF]
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S. Zaina, L. Pettersson, A. B. Thomsen, C.-M. Chai, Z. Qi, J. Thyberg, and J. Nilsson Shortened Life Span, Bradycardia, and Hypotension in Mice with Targeted Expression of an Igf2 Transgene in Smooth Muscle Cells Endocrinology, June 1, 2003; 144(6): 2695 - 2703. [Abstract] [Full Text] [PDF]
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J.-W. Chen, T. Ledet, H. Orskov, N. Jessen, S. Lund, J. Whittaker, P. De Meyts, M. B. Larsen, J. S. Christiansen, and J. Frystyk A highly sensitive and specific assay for determination of IGF-I bioactivity in human serum Am J Physiol Endocrinol Metab, June 1, 2003; 284(6): E1149 - E1155. [Abstract] [Full Text] [PDF]
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T. Kobayashi and K. Kamata Short-term insulin treatment and aortic expressions of IGF-1 receptor and VEGF mRNA in diabetic rats Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1761 - H1768. [Abstract] [Full Text] [PDF]
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E. S. Leinonen, J. T. Salonen, R. M. Salonen, R. A. Koistinen, P. J. Leinonen, S. S. Sarna, and M.-R. Taskinen Reduced IGFBP-1 Is Associated With Thickening of the Carotid Wall in Type 2 Diabetes Diabetes Care, October 1, 2002; 25(10): 1807 - 1812. [Abstract] [Full Text] [PDF]
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B. Askari, M. A. Carroll, M. Capparelli, F. Kramer, R. G. Gerrity, and K. E. Bornfeldt Oleate and Linoleate Enhance the Growth-promoting Effects of Insulin-like Growth Factor-I through a Phospholipase D-dependent Pathway in Arterial Smooth Muscle Cells J. Biol. Chem., September 20, 2002; 277(39): 36338 - 36344. [Abstract] [Full Text] [PDF]
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J. L. Hall, G. H. Gibbons, and J. C. Chatham IGF-I promotes a shift in metabolic flux in vascular smooth muscle cells Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E465 - E471. [Abstract] [Full Text] [PDF]
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J. Frystyk, T. Ledet, N. Moller, A. Flyvbjerg, and H. Orskov Cardiovascular Disease and Insulin-Like Growth Factor I Circulation, August 20, 2002; 106(8): 893 - 895. [Full Text] [PDF]
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 A. V. Moses, M. A. Jarvis, C. Raggo, Y. C. Bell, R. Ruhl, B. G. M. Luukkonen, D. J. Griffith, C. L. Wait, B. J. Druker, M. C. Heinrich, et al. Kaposi's Sarcoma-Associated Herpesvirus-Induced Upregulation of the c-kit Proto-Oncogene, as Identified by Gene Expression Profiling, Is Essential for the Transformation of Endothelial Cells J. Virol., August 15, 2002; 76(16): 8383 - 8399. [Abstract] [Full Text] [PDF]
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W. Che, N. Lerner-Marmarosh, Q. Huang, M. Osawa, S. Ohta, M. Yoshizumi, M. Glassman, J.-D. Lee, C. Yan, B. C. Berk, et al. Insulin-Like Growth Factor-1 Enhances Inflammatory Responses in Endothelial Cells: Role of Gab1 and MEKK3 in TNF-{alpha}-Induced c-Jun and NF-{kappa}B Activation and Adhesion Molecule Expression Circ. Res., June 14, 2002; 90(11): 1222 - 1230. [Abstract] [Full Text] [PDF]
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M. Zhang, E. P. Smith, H. Kuroda, W. Banach, S. D. Chernausek, and J. A. Fagin Targeted Expression of a Protease-resistant IGFBP-4 Mutant in Smooth Muscle of Transgenic Mice Results in IGFBP-4 Stabilization and Smooth Muscle Hypotrophy J. Biol. Chem., June 7, 2002; 277(24): 21285 - 21290. [Abstract] [Full Text] [PDF]
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Y. G. Amaar, G. R. Thompson, T. A. Linkhart, S.-T. Chen, D. J. Baylink, and S. Mohan Insulin-like Growth Factor-binding Protein 5 (IGFBP-5) Interacts with a Four and a Half LIM Protein 2 (FHL2) J. Biol. Chem., March 29, 2002; 277(14): 12053 - 12060. [Abstract] [Full Text] [PDF]
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 A. K. Berfield and C. K. Abrass IGF-1 Induces Foam Cell Formation in Rat Glomerular Mesangial Cells J. Histochem. Cytochem., March 1, 2002; 50(3): 395 - 403. [Abstract] [Full Text] [PDF]
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S. Zaina, L. Pettersson, B. Ahren, L. Branen, A. B. Hassan, M. Lindholm, R. Mattsson, J. Thyberg, and J. Nilsson Insulin-like Growth Factor II Plays a Central Role in Atherosclerosis in a Mouse Model J. Biol. Chem., February 1, 2002; 277(6): 4505 - 4511. [Abstract] [Full Text] [PDF]
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W. R. P. Agema, J. W. Jukema, S. N. Pimstone, and J. J. P. Kastelein Genetic aspects of restenosis after percutaneous coronary interventions;towards more tailored therapy Eur. Heart J., November 2, 2001; 22(22): 2058 - 2074. [PDF]
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B. Gonzalez, S. Lamas, and E. M. Melian Cooperation between Low Density Lipoproteins and IGF-I in the Promotion of Mitogenesis in Vascular Smooth Muscle Cells Endocrinology, November 1, 2001; 142(11): 4852 - 4860. [Abstract] [Full Text] [PDF]
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 A. Bayes-Genis, C. A. Conover, M. T. Overgaard, K. R. Bailey, M. Christiansen, D. R. Holmes Jr., R. Virmani, C. Oxvig, and R. S. Schwartz Pregnancy-Associated Plasma Protein A as a Marker of Acute Coronary Syndromes N. Engl. J. Med., October 4, 2001; 345(14): 1022 - 1029. [Abstract] [Full Text] [PDF]
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E. P. Smith, A. Kamyar, W. Niu, J. Wang, B. Cercek, S. D. Chernausek, and J. A. Fagin IGF-Binding Protein-4 Expression and IGF-Binding Protein-4 Protease Activity Are Regulated Coordinately in Smooth Muscle During Postnatal Development and After Vascular Injury Endocrinology, October 1, 2001; 142(10): 4420 - 4427. [Abstract] [Full Text] [PDF]
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A. Bayes-Genis, R. S. Schwartz, D. A. Lewis, M. T. Overgaard, M. Christiansen, C. Oxvig, K. Ashai, D. R. Holmes Jr, and C. A. Conover Insulin-Like Growth Factor Binding Protein-4 Protease Produced by Smooth Muscle Cells Increases in the Coronary Artery After Angioplasty Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 335 - 341. [Abstract] [Full Text] [PDF]
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 N. Vaessen, P. Heutink, J. A. Janssen, J. C. M. Witteman, L. Testers, A. Hofman, S. W. J. Lamberts, B. A. Oostra, H. A. P. Pols, and C. M. van Duijn A Polymorphism in the Gene for IGF-I: Functional Properties and Risk for Type 2 Diabetes and Myocardial Infarction Diabetes, March 1, 2001; 50(3): 637 - 642. [Abstract] [Full Text]
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L. Dow and S. Ebrahim Commentary: Lung function and risk of fatal and non-fatal stroke--The Copenhagen City Heart Study Int. J. Epidemiol., February 1, 2001; 30(1): 152 - 153. [Full Text] [PDF]
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 C. Muller, A. Reddert, S. Wassmann, K. Strehlow, M. Bohm, and G. Nickenig Insulin-like growth factor induces up-regulation of AT1-receptor gene expression in vascular smooth muscle cells Journal of Renin-Angiotensin-Aldosterone System, September 1, 2000; 1(3): 273 - 277. [Abstract] [PDF]
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M. J. Kluk and T. Hla Role of the Sphingosine 1-Phosphate Receptor EDG-1 in Vascular Smooth Muscle Cell Proliferation and Migration Circ. Res., September 14, 2001; 89(6): 496 - 502. [Abstract] [Full Text] [PDF]
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H. Chen, D. Li, T. Saldeen, and J. L. Mehta Transforming Growth Factor-{beta}1 Modulates Oxidatively Modified LDL-Induced Expression of Adhesion Molecules: Role of LOX-1 Circ. Res., December 7, 2001; 89(12): 1155 - 1160. [Abstract] [Full Text] [PDF]
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