doi: 10.1161/01.RES.0000038996.97287.9A
© 2002 American Heart Association, Inc.
Editorials |
Diverse Origin of Intimal Cells
Smooth Muscle Cells, Myofibroblasts, Fibroblasts, and Beyond?
From the Jefferson Heart Institute (A.Z., Y.S.), Thomas Jefferson University, Philadelphia, Pa, and GlaxoSmithKline (A.Z., A.G.J.), King of Prussia, Pa.
Correspondence to Andrew Zalewski, MD, GlaxoSmithKline, 709 Swedeland Rd, UW2900, PO Box 1539, King of Prussia, PA 19406. E-mail andrew.2.zalewski{at}gsk.com
Key Words: intima • smooth muscle cells • fibroblasts • remodeling • atherosclerosis
The formation of vascular lesions is invariably associated with the accumulation of mesenchymal cells and their products in the intima, which either compromise the vessel lumen or contribute to retention of atherogenic molecules (reviewed in References 1 and 2).1,2 As a result, pathological intimal hyperplasia is pivotal in the development of a wide range of clinical conditions, which are associated with increased cardiovascular morbidity and mortality. Nonetheless, the origin of intimal cells has remained a controversial issue in vascular biology and clinical cardiology. In addition to the expansion of preexisting intimal cells, the initial hypothesis argued for phenotypic modulation of medial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype (dedifferentiation), resulting in their migration into the intima.3,4 Several recent investigations, however, have shed new light on the mechanisms of arterial remodeling, coronary restenosis after transcatheter interventions, and vein graft changes after arterialization, which are accompanied by marked alterations in cellular composition of the affected vessel. Understanding how the vasculature alters its composition holds the key to discerning vascular responses under physiological and pathological conditions (Figure 1). In a recent issue of Circulation Research, Hu and colleagues5 join this quest, focusing on the origin of intimal cells during vein graft remodeling. In contrast to numerous observations after arterial injury, there are relatively few studies of vein graft remodeling under dyslipidemic conditions, making the analysis of vein grafts in apoE-deficient mice clearly relevant. In different types of transgenic animals, the authors demonstrated that intima of venous isografts appeared to contain SMC-like cells originating from both donor and recipient, with no apparent contribution of bone marrow-derived cells. These findings suggest vascular-bed dependent differences in the mechanisms of repair and remodeling. They also underscore the diverse cellular origin of intimal hyperplasia, which may originate from medial SMCs, poorly differentiated vascular fibroblasts, or even nonvascular sources.
|
Diversity of Vascular SMCs
Intravessel Differences
Mature tunica media contains layers of cells that express several SMC markers acquired during development (eg, 
-SM actin, SM myosin heavy chain). Despite the appearance of cellular homogeneity in situ, isolation of medial cells yields subsets with different morphology, growth, and varying expression of growth regulatory genes (eg, ERK1/ERK2).6 For example, the subendothelial layer of bovine pulmonary artery contains cells that exhibit robust proliferation and autonomous growth, which is reminiscent of the fetal SMC phenotype. A small fraction (
10%) of medial SMCs lacks muscle markers (nonmuscle cells), resembling fibroblasts that are particularly responsive to growth stimuli.7,8 Because direct isolation of distinct populations of SMCs is fraught with technical difficulties, others have characterized SMC clones originating from individual cultured cells. This approach identified distinct subsets of SMCs, which differ in regard to morphology, growth, and migration.9 The above observations confirm cellular heterogeneity of normal vessels, as assessed by independent methodologies, in different vascular beds (eg, aorta, pulmonary artery, saphenous vein) and among several species. The involvement of selected cellular components in intimal hyperplasia has been inferred from the ability of only some cells to respond to stimuli in vitro, their accumulation in injury-induced intima, and the differences in gene expression between neointimal cells and medial SMCs.7–10 In this context, the findings by Hu et al5 would benefit from further identification of specific progenitor(s) of SMC-like cells noted in the intima of remodeled vein grafts.
The above experimental findings are consistent with the hypothesis of a clonal origin of SMCs in human arterial lesions.11 The studies of X-chromosome inactivation patterns suggest that SMCs in atherosclerotic plaque may arise from the preexisting group of cells (developmental patch).12 Other possibilities include selection of a rare cell (lineage selection) or random cell mutation.13,14
Intervessel Differences
Site-specific differences in SMC characteristics have been reported among noncoronary vascular beds,15 although only a few studies specifically focused on the attributes of coronary SMCs. Coronary arteries have a distinct developmental origin, whereby their SMCs and adventitial/perivascular fibroblasts arise from common proepicardial progenitors, which undergo epithelial to mesenchymal differentiation in developing hearts in situ (Figure 2).16,17 Postnatal coronary SMCs display a highly differentiated phenotype, retaining several muscle markers in culture.18,19 Comparisons of freshly isolated coronary and noncoronary SMCs reveal differences in growth, collagen synthesis, and LDL degradation, which all suggest quantitatively lesser responses of coronary SMCs. Low expression of 5ß1 integrin (fibronectin receptor) on coronary SMCs, compared with noncoronary counterparts, may confer some coronary SMC characteristics (eg, low growth, advanced differentiation).20 The highly differentiated phenotype of coronary SMCs offers a protective mechanism, preventing early formation of occlusive lesions in the coronary vasculature. Other homeostatic properties of the intact coronary media include high expression of superoxide dismutase and tissue inhibitors of matrix metalloproteinase (TIMP-1/-2), which reduce oxidative stress and cell migration, respectively.21,22 Because the development of a more permissive SMC phenotype is associated with the increase in 5ß1 integrin, it remains to be determined whether the preselection of individual clone(s) of coronary SMCs takes place under clinically relevant conditions (eg, dyslipidemia, diabetes mellitus).20
|
Vascular Fibroblasts
Adventitial Remodeling
Adventitial fibroblasts generate high levels of superoxide anion, regulated by a key vascular oxidase, NAD(P)H oxidase.23–25 The augmented oxidative stress may represent an important mechanism by which the coronary fibroblast phenotype is modified, resulting in redox-dependent growth and gene expression.25 Observations from a porcine model suggest that adventitial fibroblasts exhibit intense proliferation followed by extracellular matrix synthesis after dissecting medial injury.26–28 The activation of adventitial fibroblasts is not unique to coronary vasculature, as it has been also noted in other models of arterial repair. Not unlike wound fibroblasts, they acquire SMC markers (eg, -SM actin), becoming myofibroblasts. The accumulation of a collagenous matrix and stress fiber containing adventitial myofibroblasts may contribute to constrictive remodeling of nonstented arteries.
Fibroblast Migration
The most controversial issue to date has been the possibility that activated fibroblasts migrate from the sites of their origin. Adventitial involvement in vascular remodeling has been implicated even in the absence of a direct endoluminal injury (Table).29–34 Labeling of proliferating adventitial fibroblasts with bromodeoxyuridine allowed for more direct tracing of their translocation to the intima.26,27 Although suggestive of the adventitia-to-intima migration, this approach cannot exclude labeling of a few proliferating (and then migrating) clones of medial SMCs. Subsequent observations in noncoronary vascular beds have provided additional support for fibroblast contribution to intimal formation. Labeling of perivascular fibroblasts days before surgical interposition of the saphenous vein graft in the arterial system is followed by the appearance of these cells in the intima.35 The loss of cellular content in the media due to apoptosis after grafting (particularly in the mouse model) makes attractive the hypothesis that at least some neointimal cells originate from perivascular/adventitial fibroblasts. Although increased expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 observed in activated adventitial fibroblasts in other experimental models provides a mechanistic explanation for their migration due to gelatinolytic and elastolytic activities, this possibility has not been explored in the study by Hu et al.5,22,36 In addition, downregulation of constitutively expressed TIMPs in the media (eg, aging, response to grafting) may contribute to cellular remodeling of the vessel.22,37
|
Cytoskeletal Changes
The expression of several cytoskeletal proteins is often used to determine cell origin in the remodeled vessel. Unfortunately, a number of these initially believed to be SMC-specific stains (eg, -SM actin, desmin) were later found in cells of fibroblastic origin during organ remodeling. The changes in cytoskeletal proteins in activated adventitial fibroblasts resemble the sequential expression of differentiation markers in the process of SMC maturation during development.17,38 The autocrine expression of TGFß1 has been associated with the appearance of adventitial myofibroblasts, expressing -SM actin, to a lesser degree desmin, and possibly other SMC markers (eg, SM22).39,40 Smoothelin, a novel marker acquired at the end of SMC maturation, has been found only in the media and neointima but not in the adventitia.41 These findings suggest that either fibroblast migration to the intima is negligible or that upon translocation of these cells, the process of transdifferentiation continues with the appearance of late markers of SMCs in the intima. Additional studies are required to define molecular mechanisms and local factors that override repressing activity that normally prevents transdifferentiation of fibroblasts to SMCs.42 Taking into consideration the common origin of coronary mesenchymal cells and the overall biological properties of coronary fibroblasts, it is suggested that the terms such as fibroblasts, myofibroblasts, or SMCs represent a continuum of the differentiation process.
Bone Marrow-Derived Intimal Cells
Additional sources of vascular myofibroblasts may include cells derived from the bone marrow. Mesenchymal stromal cells of the bone marrow have the ability to acquire characteristics of several more differentiated cells (eg, osteoblasts, adipocytes).43 Hematopoietic cells (monocyte-derived) or stromal cells of the bone marrow can also transdifferentiate to myofibroblasts in vitro.44,45 Whether this occurs in vivo remains the subject of disparate reports, with findings by Hu et al5 unable to confirm the presence of bone marrow- derived cells in intima of atherosclerotic vein grafts (mouse model). This contrasts with recent studies of arterial injury, heterotopic cardiac transplantation, and arterial atherosclerosis where SMC-like cells originating from hematopoietic stem cells were identified in intima (mouse models).46,47 If bone marrow cells participate in pathological remodeling in other species, including humans, then the understanding of molecular mechanisms underlying their homing in lesion-prone segments and transdifferentiation to proatherogenic phenotype would be of clear therapeutic value.
Conclusions
There is growing recognition that the cellular constituents of vascular beds display diverse intravessel and intervessel characteristics. Ample evidence indicates the biological uniqueness of intimal cells, which may originate from highly distinct subset(s) of medial SMCs or nonmuscle cells. Vascular remodeling appears to have unique characteristics in coronary and noncoronary arterial beds as well as venous bypass grafts. The understanding of these processes goes far beyond intellectual curiosity, because it raises the prospect of defining better potential therapeutic targets for the prevention of intimal lesion formation. There are, however, major challenges related to uncertain relevance of current animal models of atherosclerosis to clinical conditions. The latter clearly includes both coronary and noncoronary cell responses to long-term stimulation, such as low-grade inflammation, diabetes mellitus, dyslipidemia, and specific immune responses, which are often lacking in the preclinical studies. Only by launching an integrated basic and clinical research initiative ("from mouse to man") can recent advances in the understanding of the mechanisms of vascular repair and remodeling be translated to the development of novel systemic therapies as well as locally applied therapeutics.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
References
1. Schwartz SM, deBlois D, O’Brien ERM. The intima: soil for atherosclerosis and restenosis. Circ Res. 1995; 77: 445–465.
2. Williams KJ, Tabas I. The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol. 1995; 15: 551–561.
3. Campbell GR, Campbell JH, Manderson JA, Horrigan S, Rennick RE. Arterial smooth muscle: a multifunctional mesenchymal cell. Arch Pathol Lab Med. 1988; 112: 977–986.[Medline] [Order article via Infotrieve]
4. Thyberg J, Hedin U, Sjolund M, Palmberg L, Bottger BA. Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis. 1990; 10: 966–990.
5. Hu Y, Mayr M, Metzler B, Erdel M, Davison F, Xu Q. Both donor and recipient origins of smooth muscle cells in vein graft atherosclerotic lesions. Circ Res. 2002; 91: e13–e20.[Medline] [Order article via Infotrieve]
6. Frid MG, Aldashev AA, Nemenoff RA, Higashito R, Wescott JY, Stenmark KR. Subendothelial cells from normal bovine arteries exhibit growth and constitutively activated intracellular signaling. Arterioscler Thromb Vasc Biol. 1999; 19: 2884–2893.
7. Holifield B, Helgason T, Jemelka S, Taylor A, Nevran S, Allen J, Seidel C. Differentiated vascular myocytes: are they involved in neointimal formation? J Clin Invest. 1996; 97: 814–825.[Medline] [Order article via Infotrieve]
8. Frid MG, Aldashev AA, Dempsey EC, Stenmark KR. Smooth muscle cells isolated from discrete compartments of the mature vascular media exhibit unique phenotypes and distinct growth capabilities. Circ Res. 1997; 81: 940–952.
9. Bochaton-Piallat ML, Ropraz P, Gabbiani F, Gabbiani G. Phenotypic heterogeneity of rat arterial smooth muscle clones: implications for the development of experimental intimal thickening. Arterioscler Thromb Vasc Biol. 1996; 16: 815–820.
10. Majesky MW, Giachelli CM, Reidy MA, Schwartz SM. Rat carotid neointimal smooth muscle cells reexpress a developmentally regulated mRNA phenotype during repair of arterial injury. Circ Res. 1992; 71: 759–768.
11. Benditt EP, Benditt JM. Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci U S A. 1973; 70: 1753–1756.
12. Murray CE, Gipaya CT, Bartosek T, Benditt EP, Schwartz SM. Monoclonality of smooth muscle cells in human atherosclerosis. Am J Pathol. 1997; 151: 697–705.[Abstract]
13. McCaffrey TA, Du B, Consigli S, Szabo P, Bray PJ, Hartner L, Weksler BB, Sanborn TA, Bergman G, Bush HL Jr. Genomic instability in the type II TGFß1 receptor gene in atherosclerotic and restenotic vascular cells. J Clin Invest. 1997; 100: 2182–2188.[Medline] [Order article via Infotrieve]
14. Casalone R, Granata P, Minelli E, Portentoso P, Giudici A, Righi R, Castelli P, Socrate A, Frigerio B. Cytogenetic analysis reveals clonal proliferation of smooth muscle cells in atherosclerotic plaques. Hum Genet. 1991; 87: 139–143.[CrossRef][Medline] [Order article via Infotrieve]
15. Yang Z, Oemar BS, Carrel T, Kipfer B, Julmy F, Luscher TF. Different proliferative properties of smooth muscle cells of human arterial and venous bypass vessels. Circulation. 1998; 97: 181–187.
16. Dettman RW, Denetclaw W, Ordahl CP, Bristow J. Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol. 1998; 193: 169–181.[CrossRef][Medline] [Order article via Infotrieve]
17. Landerholm TE, Dong XR, Lu J, Belaguli ND, Schwartz RJ, Majesky MW. A role for serum response factor in coronary smooth muscle differentiation from proepicardial cells. Development. 1999; 126: 2053–2062.[Abstract]
18. Christen T, Bochaton-Piallat ML, Neuville P, Rensen S, Redard M, van Eys G, Gabbiani G. Cultured porcine coronary artery smooth muscle cells: a new model with advanced differentiation. Circ Res. 1999; 85: 99–107.
19. Patel S, Shi Y, Niculescu R, Chung E, Martin JL, Zalewski A. Characteristics of coronary smooth muscle cells and adventitial fibroblasts. Circulation. 2000; 101: 524–532.
20. Davenpeck KL, Marcinkiewicz C, Wang D, Niculescu R, Shi Y, Martin JL, Zalewski A. Regional differences in integrin expression: role of 5ß1 in regulating smooth muscle cell functions. Circ Res. 2001; 88: 352–358.
21. Strålin P, Karlson K, Johansson BO, Marklund S. The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arterioscler Thromb Vasc Biol. 1995; 15: 2032–2036.
22. Shi Y, Patel S, Niculescu R, Chung W, Desrochers P, Zalewski A. Role of matrix metalloproteinases and their tissue inhibitors in the regulation of coronary cell migration. Arterioscler Thromb Vasc Biol. 1999; 19: 1150–1155.
23. Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT. Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: enhancement by angiotensin II. Proc Natl Acad Sci U S A. 1997; 94: 14483–14488.
24. Wang HD, Pagano PJ, Du Y, Cayatte AJ, Quinn MT, Brecher P, Cohen RA. Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric oxide. Circ Res. 1998; 82: 810–818.
25. Shi Y, Niculescu R, Wang D, Patel S, Davenpeck KL, Zalewski A. Increased NAD(P)H oxidase and reactive oxygen species in coronary arteries after balloon injury. Arterioscler Thromb Vasc Biol. 2001; 21: 739–745.
26. Scott NA, Cipolla GD, Ross CE, Dunn B, Martin FH, Simonet L, Wilcox JN. Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries. Circulation. 1996; 93: 2178–2187.
27. Shi Y, O’Brien JE, Fard A, Mannion JD, Zalewski A. Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation. 1996; 94: 1655–1664.
28. Shi Y, O’Brien JE Jr, Ala-Kokko L, Chung WS, Mannion JD, Zalewski A. Origin of extracellular matrix synthesis during coronary repair. Circulation. 1997; 95: 997–1006.
29. Nakata Y, Shionoya S. Vascular lesions due to obstruction of the vasa vasorum. Nature. 1966; 212: 1258–1259.[CrossRef]
30. Booth RFG, Martin JF, Honey AC, Hassall DG, Beesley JE, Moncada S. Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation. Atherosclerosis. 1989; 76: 257–268.[CrossRef][Medline] [Order article via Infotrieve]
31. Barker SGE, Talbert A, Cottam S, Baskerville PA, Martin JF. Arterial intimal hyperplasia after occlusion of the adventitial vasa vasorum in the pig. Arterioscler Thromb. 1993; 13: 70–77.
32. Prescott MF, McBride CK, Court M. Development of intimal lesions after leukocyte migration into the vessel wall. Am J Pathol. 1989; 135: 835–846.[Abstract]
33. Shimokawa H, Ito A, Fukumoto Y, Kadokami T, Nakaike R, Sakata M, Takayanagi T, Egashira K, Takeshita A. Chronic treatment with interleukin-1ß induces coronary intimal lesions and vasospastic responses in pigs in vivo. J Clin Invest. 1996; 97: 769–776.[Medline] [Order article via Infotrieve]
34. Miyata K, Shimokawa H, Kandabashi T, Higo T, Morishige K, Eto Y, Egashira K, Kaibuschi K, Takeshita A. Rho-kinase is involved in macrophage-mediated formation of coronary vascular lesions in pigs in vivo. Arterioscler Thromb Vasc Biol. 2000; 20: 2351–2358.
35. Shi Y, O’Brien JE, Mannion JD, Morrison RC, Fard A, Chung WS, Zalewski A. Remodeling of autologous saphenous vein grafts: the role of perivascular myofibroblasts. Circulation. 1997; 95: 2684–2693.
36. Godin D, Ivan E, Johnson C, Magid R, Galis ZS. Remodeling of carotid artery is associated with increased expression of matrix metalloproteinases in mouse blood flow cessation model. Circulation. 2000; 102: 2861–2866.
37. Ashcroft GS, Herrick SE, Tarnuzzer RW, Horan MA, Schultz GS, Ferguson MWJ. Human ageing impairs injury-induced in vivo expression of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -2 proteins and mRNA. J Pathol. 1997; 183: 169–176.[CrossRef][Medline] [Order article via Infotrieve]
38. Owens G. Regulation of differentiation of vascular smooth muscle cells. Physiol Rev. 1995; 75: 487–517.
39. Shi Y, O’Brien JE, Fard A, Zalewski A. Transforming growth factor-ß1 expression and myofibroblast formation during arterial repair. Arterioscler Thromb Vasc Biol. 1996; 16: 1298–1305.
40. Faggin E, Puato M, Zardo L, Franch R, Millino C, Sarinella F, Pauletto P, Sartore S, Chiavegato A. Smooth muscle-specific SM22 protein is expressed in the adventitial cells of balloon-injured rabbit carotid artery. Arterioscler Thromb Vasc Biol. 1999; 19: 1393–1404.
41. Christen T, Verin V, Bochaton-Piallat M-L, Popowski Y, Ramaekers F, Debruyne P, Camenzind E, van Eys G, Gabbiani G. Mechanisms of neointima formation and remodeling in the porcine coronary artery. Circulation. 2001; 103: 882–888.
42. Hautmann M, Adam PJ, Owens GK. Similarities and differences in smooth muscle -actin induction by TGF-ß in smooth muscle versus non-smooth muscle cells. Arterioscler Thromb Vasc Biol. 1999; 19: 2049–2058.
43. Pereira RF, Halford KW, O’Hara MD, Leeper DB, Sokolow BP, Pollard MD, Bagasra O, Prockop DJ. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A. 1995; 92: 4857–4861.
44. Campbell JH, Efendy JL, Chih-Lu H, Girjes AA, Campbell GR. Haemopoietic origin of myofibroblasts formed in the peritoneal cavity in response to a foreign body. J Vasc Res. 2000; 37: 364–371.[CrossRef][Medline] [Order article via Infotrieve]
45. Bonanno E, Ercoli L, Missori P, Rocchi G, Spagnoli LG. Homogenous stromal cell population form normal human adult bone marrow expressing -smooth muscle actin filament. Lab Invest. 1994; 71: 308–315.[Medline]
[Order article via Infotrieve]
46. Han CI, Campbell GR, Campbell JH. Circulating bone marrow cells can contribute to neointimal formation. J Vasc Res. 2001; 38: 113–119.[CrossRef][Medline] [Order article via Infotrieve]
47. Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Nagai R. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 2002; 8: 403–409.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  R. Foth, T. Quentin, I. Michel-Behnke, M. Vogt, T. Kriebel, A. Kreischer, W. Ruschewski, T. Paul, and M. Sigler Immunohistochemical Characterization of Neotissues and Tissue Reactions to Septal Defect-Occlusion Devices Circ Cardiovasc Interv, April 1, 2009; 2(2): 90 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Vaahtomeri, E. Ventela, K. Laajanen, P. Katajisto, P.-J. Wipff, B. Hinz, T. Vallenius, M. Tiainen, and T. P. Makela Lkb1 is required for TGF{beta}-mediated myofibroblast differentiation J. Cell Sci., November 1, 2008; 121(21): 3531 - 3540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.J.W Evans, P.V Lawford, J Gunn, D Walker, D.R Hose, R.H Smallwood, B Chopard, M Krafczyk, J Bernsdorf, and A Hoekstra The application of multiscale modelling to the process of development and prevention of stenosis in a stented coronary artery Phil Trans R Soc A, September 28, 2008; 366(1879): 3343 - 3360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Iwata and M. Sata Origin of Cells That Contribute to Neointima Growth Circulation, June 17, 2008; 117(24): 3060 - 3061. [Full Text] [PDF]
|
|
|
|
 |
|
 C. D Owens, K. J Ho, and M. S Conte Lower extremity vein graft failure: a translational approach Vascular Medicine, February 1, 2008; 13(1): 63 - 74. [Abstract] [PDF]
|
|
|
|
 |
|
 F. A. Auger, P. D'Orleans-Juste, and L. Germain Adventitia contribution to vascular contraction: Hints provided by tissue-engineered substitutes Cardiovasc Res, September 1, 2007; 75(4): 669 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hinz, S. H. Phan, V. J. Thannickal, A. Galli, M.-L. Bochaton-Piallat, and G. Gabbiani The Myofibroblast: One Function, Multiple Origins Am. J. Pathol., June 1, 2007; 170(6): 1807 - 1816. [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]
|
|
|
|
 |
|
 J.-H. Parmentier, C. Zhang, A. Estes, S. Schaefer, and K. U. Malik Essential role of PKC-{zeta} in normal and angiotensin II-accelerated neointimal growth after vascular injury Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1602 - H1613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sainz and M. Sata Maintenance of Vascular Homeostasis by Bone Marrow-Derived Cells. Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1196 - 1197. [Full Text] [PDF]
|
|
|
|
|
|
K. Schafer, M. R. Schroeter, C. Dellas, M. Puls, M. Nitsche, E. Weiss, G. Hasenfuss, and S. V. Konstantinides Plasminogen Activator Inhibitor-1 From Bone Marrow-Derived Cells Suppresses Neointimal Formation After Vascular Injury in Mice Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1254 - 1259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sata Role of Circulating Vascular Progenitors in Angiogenesis, Vascular Healing, and Pulmonary Hypertension: Lessons From Animal Models Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1008 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Vascular-wall remodeling of 3 human bypass vessels: organ culture and smooth muscle cell properties. J. Thorac. Cardiovasc. Surg., March 1, 2006; 131(3): 651 - 658.
|
|
|
|
 |
|
 V. da Cunha, B. Martin-McNulty, J. Vincelette, L. Zhang, J. C. Rutledge, D. W. Wilson, R. Vergona, M. E. Sullivan, and Y.-X. Wang Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice J. Lipid Res., March 1, 2006; 47(3): 476 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Newby Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates Cardiovasc Res, February 15, 2006; 69(3): 614 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Dobreva, G. Waeber, R. W. James, and C. Widmann Interleukin-8 Secretion by Fibroblasts Induced by Low Density Lipoproteins Is p38 MAPK-dependent and Leads to Cell Spreading and Wound Closure J. Biol. Chem., January 6, 2006; 281(1): 199 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chandiwal, V. Balasubramanian, Z. K. Baldwin, M. S. Conte, and L. B. Schwartz Gene Therapy for the Extension of Vein Graft Patency: A Review Vascular and Endovascular Surgery, January 1, 2005; 39(1): 1 - 14. [Abstract] [PDF]
|
|
|
|
 |
|
 A. C. Newby Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture Physiol Rev, January 1, 2005; 85(1): 1 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sata and R. Nagai Origin of Neointimal Cells in Autologous Vein Graft Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1147 - 1149. [Full Text] [PDF]
|
|
|
|
|
|
B. C. Cooley Murine Model of Neointimal Formation and Stenosis in Vein Grafts Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1180 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tanaka, M. Sata, Y. Hirata, and R. Nagai Diverse Contribution of Bone Marrow Cells to Neointimal Hyperplasia After Mechanical Vascular Injuries Circ. Res., October 17, 2003; 93(8): 783 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hao, G. Gabbiani, and M.-L. Bochaton-Piallat Arterial Smooth Muscle Cell Heterogeneity: Implications for Atherosclerosis and Restenosis Development Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1510 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, A. Zalewski, Y. Liu, T. Mazurek, S. Cowan, J. L. Martin, S. M. Hofmann, H. Vlassara, and Y. Shi Diabetes-Induced Oxidative Stress and Low-Grade Inflammation in Porcine Coronary Arteries Circulation, July 29, 2003; 108(4): 472 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Agarwal and M. S. Segal Intimal Exuberance: Veins in Jeopardy Am. J. Pathol., June 1, 2003; 162(6): 1759 - 1761. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||