This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walsh, K. Articles by Kim, H.-S. Search for Related Content PubMed PubMed Citation Articles by Walsh, K. Articles by Kim, H.-S. Related Collections Animal models of human disease Apoptosis Gene regulation Other arteriosclerosis Other Vascular biology

(Circulation Research. 2000;87:184.)
© 2000 American Heart Association, Inc.

Review

Vascular Cell Apoptosis in Remodeling, Restenosis, and Plaque Rupture

Kenneth Walsh, Roy C. Smith, Hyo-Soo Kim

From the Divisions of Cardiovascular Research and Vascular Medicine, St. Elizabeth’s Medical Center, and the Program in Cell, Molecular and Developmental Biology, Sackler School of Biomedical Studies, Tufts University School of Medicine, Boston, Mass.

Correspondence to Dr Kenneth Walsh, Division of Cardiovascular Research, St. Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA 02135. E-mail kwalsh@world.std.com or kwalsh{at}opal.tufts.edu

Key Words: remodeling • atherosclerosis • restenosis • apoptosis

	Introduction

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
This Review is part of a thematic series on Apoptosis in the Cardiovascular System, which includes the following articles: Apoptosis and Heart Failure: A Critical Review of the Literature

Vascular Cell Apoptosis in Remodeling, Restenosis, and Plaque Rupture

Apoptosis During Cardiovascular Development Myocyte Apoptosis in Ischemic Heart Disease Endothelial Cell Apoptosis in Angiogenesis and Vessel RegressionRichard Kitsis, Guest Editor

Apoptotic death of vascular cells is a prominent feature of blood vessel remodeling that occurs during normal development and fibroproliferative disorders of the vessel wall. This review summarizes a large number of studies that have provided evidence for apoptotic cell death in the vasculature. We also describe reports that shed light on the molecular mechanisms that may control this process. Finally, we highlight the relatively small number of studies that suggest a function for vascular cell apoptosis in controlling the morphology and cellular composition of the blood vessel wall.

	Vascular Cell Apoptosis During Development and Flow-Induced Vessel Remodeling

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
A number of studies have demonstrated apoptotic death of vascular cells in vessels that remodel postnatally. Regionalized apoptosis has been found in vascular smooth muscle cells (VSMCs) during the regression and closure of the human ductus arteriosus before birth¹ and in VSMCs and endothelial cells of the arteries and veins of the umbilical cord, which are subject to dramatic hemodynamic changes at birth.² Evidence of VSMC apoptosis in the human neonate has also been found at the branch points of the great arteries arising from the aortic arch when they are exposed to a disturbed blood flow, whereas VSMC apoptosis was not observed in the aorta when a normal flow pattern is maintained.² Finally, VSMC apoptosis has been observed during the remodeling of the abdominal aorta in lambs, resulting from the large decrease in blood flow that occurs after the loss of the placenta at birth.³

Vascular cell apoptosis during neonatal vascular remodeling appears to be triggered by decreased flow or by perturbation of flow at branch points that results when the organism switches oxygen exchange from the placenta to the lungs. Cell loss occurring upon flow-induced vessel remodeling has been directly demonstrated by inducing changes in flow through the carotid arteries of immature rabbits.⁴ In that experimental system, ligation of the left external carotid artery results in a marked reduction in blood flow through the common carotid artery, and this reduction correlates with a large increase in endothelial cell and VSMC apoptosis. Presumably, vascular cell apoptosis contributes to an adaptive process that allows the vessel to permanently constrict to manage the decrease in flow.

Changes in flow affect wall tension and cell matrix interactions, and it may be these factors that alter the survival characteristics of vascular cells. Consistent with this notion, VSMC apoptosis occurs when wall tension is diminished,⁵ or enhanced,⁶ or when the expression of matrix components⁷ or matrix metalloproteinases⁸ is altered. Although changes in the proapoptotic proteins Bax and Bcl-X_S are associated with flow-induced vascular remodeling,² relatively little is known about the molecular mechanisms that regulate vascular cell viability under these circumstances. Furthermore, although it makes intuitive sense that cellular elimination would be required for negative remodeling of a vessel, causal data in support of this hypothesis have not yet been provided.

	Apoptosis in Chronic Vascular Lesions

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
Apoptosis also appears to be a feature of the remodeling processes occurring in chronic inflammatory fibroproliferative disorders of the vessel wall. Numerous studies have documented VSMC apoptosis in atherectomy specimens from atherosclerotic and restenotic lesions,^{9 10 11 12} and apoptosis has also been observed in macrophages and T cells within atherosclerotic lesions.¹³ Consistent with a remodeling function, vascular cell apoptosis has also been reported to be more pronounced in advanced atherosclerotic lesions compared with regions of early intimal thickening and/or fatty streaks.¹⁴ Atherectomy specimens from patients with in-stent restenosis also display abundant apoptotic cells, and a large fraction of VSMCs are positive for cell-cycle protein expression, suggesting high levels of VSMC turnover.¹⁵ Finally, apoptosis within chronic vascular lesions is also observed in animal models including the atherosclerotic plaques of cholesterol-fed rabbits,¹⁶ the advanced vascular lesions of APOE*3-Leiden transgenic mice,¹⁷ and the aortas of hyperlipidemic ApoE- and LDL receptor–deficient mice.¹⁸

The diminished plaque cellularity of advanced lesions may be attributed to VSMC apoptosis, and it has been proposed that VSMC apoptosis eventually contributes to plaque rupture. This stems from the observation that VSMCs cultured from atherosclerotic coronary atherectomy specimens proliferate more slowly and demonstrate higher frequencies of apoptosis than VSMCs from normal vessels.^{9 19} This process may lead to plaque destabilization since apoptotic and necrotic cells have been detected in atherosclerotic plaques with a recent history of rupture²⁰ and VSMC apoptosis can be observed in the fibrous cap and underlying media of nonulcerated lesions obtained from human thoracic aorta and coronary arteries.¹³ However, causal data that could shed light on the relative importance of apoptotic cell death in plaque rupture have not been provided. Furthermore, the molecular mechanisms regulating cellular viability in chronic vascular lesions have not been defined in detail.

	Vascular Cell Apoptosis Induced by Acute Balloon Injury

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
Apoptotic VSMC death has been documented in numerous animal models of acute vascular injury. Several studies demonstrate that balloon injury of vessels induces two waves of VSMC apoptosis. Generally speaking, the first wave is a rapid burst of apoptosis in the media occurring within hours of the injury, resulting in a marked decrease in vessel wall cellularity. Initial studies in the rat carotid artery model of vascular injury demonstrated that balloon denudation leads to a rapid and relatively synchronous induction of medial VSMC apoptosis.²¹ Apoptotic marker expression in this model peaked at 1 hour after injury but is no longer evident by 4 hours after injury. The frequency of apoptotic cells correlates with the decrease in cellular density (up to 65%) that is observed within hours of injury. This rapid decrease in vessel wall cellularity occurs before the initiation of cell-cycle activity in VSMCs.²² Although the consequences of early-onset apoptosis in medial VSMCs are unknown, it could exacerbate neointima lesion formation at later time points by provoking a greater wound healing response to overcome the cellular deficit. Consistent with this notion, cells can release cytokines as they undergo apoptosis,²³ and this could enhance the proliferative response after traumatic balloon injury.

The second wave of apoptosis occurs at much later times after injury (days to weeks) and at much lower frequencies. In the rat carotid model, apoptosis at these later time points is confined to the VSMCs of the developing neointima.^{24 25} This second wave of apoptosis may limit lesion growth. It has long been known that VSMC accumulation in the neointima of injured rat carotid arteries reaches a maximal level at 2 weeks after injury, yet cellular proliferation continues for up to 12 weeks.²⁶ Presumably the rates of neointimal VSMC death and proliferation are in equilibrium from 2 weeks onward, thereby preventing any further increase in lesion size.

Rapid balloon angioplasty–induced apoptosis has also been documented in the rabbit iliac model.²¹ In this case, increased balloon-to-artery ratios produce greater frequencies of VSMC apoptosis at early time points, and this correlates with more acute cell loss.²⁷ The rapid wave of apoptosis resulting from mechanical injury appears to involve a redox-sensitive pathway, because local administration of antioxidants will minimize cell loss.²⁸ Surprisingly, analyses of diseased vessels have revealed that VSMCs of the neointima are less sensitive to rapid-onset apoptosis than are the VSMCs of the underlying media,^{27 29} suggesting that modulation of the VSMC phenotype influences angioplasty-induced apoptosis. Normocholesterolemic and hypercholesterolemic rabbits display similar profiles of early postinjury apoptosis, but hypercholesterolemia enhances apoptosis in the neointima at 2 weeks after injury.³⁰ This observation has led to the hypothesis that macrophages present in the vascular lesions of the hypercholesterolemic rabbits may contribute to VSMC turnover at later time points. Macrophage involvement has also been implicated in VSMC apoptosis observed after stent implantation in rabbit vessels.³¹

Finally, VSMC apoptosis has also been described in balloon-injured porcine coronary arteries.³² In this model, apoptosis is first observed at sites of obvious trauma at 1 hour after injury and, at later times, in the deeper layers of the media. Medial VSMC apoptosis peaks at 18 hours after injury, and lower levels of apoptosis are observed at 3 days and 7 days, but not at 14 days. The time course of apoptosis in cells of the adventitia and loose connective tissue was similar to that of medial cells.

	Regulation of Vascular Cell Viability by Bcl-2 Family Proteins

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
Cell viability is governed at the molecular level by a balance between proapoptotic and antiapoptotic signals mediated by a number of gene families, the most prominent being the Bcl-2 family. Bcl-2 family members that promote cell survival include Bcl-2, A1, and the long form of Bcl-X (Bcl-X_L), whereas Bax, Bad, and Bid function to promote apoptosis. Numerous studies have examined the role of Bcl-2 family proteins in controlling vascular cell viability. Bax expression is elevated in VSMCs of human atherosclerotic plaques, where high frequencies of apoptosis are observed.¹⁴ This is reminiscent of the situation in the neonate where vascular remodeling and vessel regression are associated with upregulation of Bax expression in VSMCs.² The protective protein Bcl-X_L is abundantly expressed in normal medial VSMCs but is downregulated after balloon injury with a time course that correlates with the early wave of apoptotic cell death.²¹ Bcl-X_L expression is also elevated in rabbit intimal VSMCs, which are more resistant to angioplasty-induced apoptosis than medial VSMCs.²⁹

The functional significance of Bcl-2 family proteins in VSMC survival has been demonstrated by acute ablation experiments. It has been shown that neointimal VSMC apoptosis can be induced in stenotic vessels by Bcl-X_L ablation using an antisense strategy, leading to a reduction in intimal thickness.²⁹ Because Bcl-X_L is preferentially expressed in neointimal VSMCs, this factor may contribute to the differential sensitivity of medial and neointimal VSMCs to balloon injury–induced apoptosis. VSMC apoptosis can also be triggered by acute ablation of Bcl-2 using an adenovirus-encoded ribozyme directed against bcl-2 mRNA, which brings about a decrease in vessel wall cellularity and reduced intimal lesion formation after balloon injury.³³ Collectively, these studies show that endogenous levels of Bcl-2 and Bcl-X_L are essential for VSMC viability, and thus, stimuli that alter Bcl-X_L or Bcl-2 expression could influence VSMC survival in the vessel wall.

In addition to the Bcl-2 family proteins, it has been suggested that the transcription factor p53 regulates vascular cell apoptosis because p53 is reported to accumulate in atherosclerotic lesions.³⁴ This factor promotes apoptosis by functioning, at least in part, as a positive regulator of Bax expression³⁵ and a negative regulator of Bcl-2 expression.³⁶ Interestingly, p53 can also promote VSMC apoptosis by increasing cell surface expression of the death ligand receptor Fas.³⁷ Forced overexpression of p53 induces VSMC apoptosis in vitro and inhibits neointima lesion formation in vivo.^{19 38} In addition to this proapoptotic function, p53 negatively regulates cell growth through its ability to induce the cyclin-dependent kinase inhibitor p21.³⁹ Consistent with expectations from in vitro studies, p53 deficiency exacerbates atherosclerotic lesion expansion in ApoE-deficient mice fed a high-fat diet⁴⁰ However, this lack of p53 has no effect on the frequency of vascular cell apoptosis within the lesions; the increase in lesion size appears to result from increased vascular cell proliferation. As a consequence of these observations, the role of p53 in controlling cell death within atherosclerotic lesions is uncertain.

	Death Receptor/Ligand Interactions in Vascular Cells

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
Members of the tumor necrosis factor receptor family may also participate in the regulation of vascular cell survival. In the vasculature, most studies to date have focused on cell death mediated by Fas/FasL signaling. The death receptor Fas is ubiquitously expressed, whereas FasL is typically expressed on the cell surface of inflammatory cells including T cells and macrophages. Fas-mediated apoptosis has been implicated as functioning mainly to downregulate inflammatory reactions. The gld and lpr strains of mice are null for functional FasL and Fas expression, respectively, and suffer from rheumatic diseases characterized by aberrant inflammation.^{41 42} That Fas-mediated apoptosis is required for the elimination of autoreactive and peripheral T cells is well established,⁴³ and spontaneous monocyte apoptosis is also controlled by Fas.^{44 45 46} Consistent with an anti-inflammatory role, FasL is expressed at sites of "immune privilege," such as eye and testis where it may inhibit inflammation by killing immune cells as they attempt to infiltrate the tissue.^{47 48} FasL within the vasculature is expressed at low levels on the surface of endothelial cells where it may serve a similar function by inhibiting adventitious leukocyte extravasation.^{49 50} In marked contrast to the anti-inflammatory function of endogenous FasL, ectopic expression of this protein in Fas-expressing cells can, in some cases, result in tissue destruction and induce inflammatory responses that are characterized by neutrophil infiltration.²³

It has been proposed that Fas-mediated apoptosis plays a role in a variety of vascular disorders including atherogenesis,^{51 52 53 54 55} allograft arteriopathy,⁵⁶ and acute inflammatory responses.⁴⁹ Because VSMCs express Fas and inflammatory cells express FasL, it is possible that Fas-mediated apoptosis contributes to atherosclerotic plaque instability.⁵⁴ The susceptibility of VSMCs to Fas-mediated cell death in vitro and in vivo has been documented in numerous studies. Cultured VSMCs undergo apoptosis after infection with a replication-defective adenoviral vector that encodes cell surface FasL.^{50 57} Consistent with its expression on the cell surface, coculture experiments reveal that FasL-expressing VSMCs kill cells in a paracrine manner. Local delivery of adenovirus encoding FasL to balloon-injured rat carotid arteries induces apoptosis in proliferating smooth muscle cells and potently inhibits intimal hyperplasia.⁵⁷ Although VSMCs are susceptible to adenovirus-encoded FasL expressed at the cell surface, they are not efficiently killed by soluble recombinant FasL or agonist anti–Fas antibody.⁵⁰ Presumably these soluble reagents are less efficient than cell surface FasL at inducing Fas clustering on the membrane of the target cell.⁵⁸ Consistent with this interpretation, VSMCs are sensitized to Fas-mediated apoptosis by interferon , which favors receptor clustering by upregulating cell surface Fas expression.^{50 54 59}

In striking contrast to VSMCs, vascular endothelial cells are normally resistant to Fas-mediated apoptosis^{51 60} and remain resistant even when Fas expression is upregulated by exposure to interferon ,^{50 60} suggesting that resistance is not due to low levels of receptor expression. The marked differences in the sensitivity of vascular cells to Fas-induced apoptosis may be mediated by the expression of cellular FLIPs (FLICE-like inhibitory proteins) that function as dominant-negative inhibitors of caspase-8 function.^{61 62} FLIP isoforms are abundantly expressed in endothelial cells where they may function to inhibit Fas-mediated cell suicide (or fratricide).⁶³ Along these lines, it is reported that FLIP expression in rat carotid VSMCs is downregulated after balloon injury and human atherosclerotic plaque VSMCs express relatively low levels of FLIP,⁶⁴ suggesting that FLIP may participate in the regulation of VSMC turnover in those lesions.

Many lines of evidence suggest that Fas-mediated cell death is important in the control of vessel wall inflammation. First, it has been shown that a deficiency in Fas-mediated apoptosis will lead to vasculitis, resulting from neutrophilic and mononuclear cell infiltrates, in some strains of gld and lpr mice.^{65 66} Second, FasL-deficient mice display enhanced mononuclear cell infiltration and intimal hyperplasia in a flow-restricted model of vascular injury that induces neointima formation in the presence of an intact endothelium.⁶⁷ Third, it has been shown that constitutive overexpression of FasL on the vascular endothelium will inhibit tumor necrosis factor-–mediated leukocyte extravasation.⁴⁹ Also, consistent with an anti-inflammatory role, ectopic FasL expression by medial VSMCs in balloon-injured arteries inhibits T cell–mediated inflammatory responses directed against adenovirus-infected cells.^{57 68} Because chronic vessel inflammation is an important component of atherogenesis, FasL may serve an atheroprotective function through its ability to kill inflammatory cells. Alternatively, dysregulated expression of the Fas signaling pathway could, under some conditions, promote atherosclerosis. For example, oxidized lipids and other oxidative stresses can sensitize endothelial cells to Fas-mediated apoptosis by downregulating FLIP expression.^{51 63} Thus, Fas-mediated apoptosis of endothelial cells may contribute to a loss of endothelium integrity in diseased vessels.

Collectively, data from mouse and other experimental systems largely support the hypothesis that Fas inhibits vascular inflammation and serves a protective role during vascular remodeling; however, causal data linking Fas-mediated apoptosis to atherogenesis and plaque rupture have not appeared to date.

	Closing Remarks

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
Vascular cell apoptosis is prevalent under conditions that promote vessel wall remodeling. On the basis of the data we have summarized here, some general statements about apoptosis of vascular cells during physiological or pathological vessel remodeling can be made. With regard to the occurrence of apoptosis within the vasculature, the following statements can be made:

Apoptotic death of VSMCs and endothelial cells has been documented during human development in vessels where flow is altered and in experimental systems of acute flow perturbation.

Apoptosis in VSMCs, endothelial cells, and inflammatory cells has been found in chronic vascular lesions of humans and animal models of atherosclerosis.

Apoptosis is also responsible for VSMC turnover in intimal lesions that form as a result of acute injury, and a rapid wave of apoptotic VSMC death contributes to the decreased cellularity in the media occurring within hours of traumatic balloon injury.

With regard to molecular control of apoptosis and vascular cell viability, the following may be said:

Apoptosis of VSMCs occurs during developmentally regulated or pathological vascular remodeling and correlates with changes in Bcl-2 family protein expression.

Bcl-X_L and Bcl-2 are essential for VSMC viability in vitro and in vivo.

The Fas/FasL system is essential for the inhibition of vessel inflammation.

Fas-mediated cell death may also play a role in atherogenesis and plaque rupture, but causal data in support of these hypotheses are lacking.

In conclusion, the data suggesting that apoptosis plays a role in developmentally regulated or pathological vessel remodeling are largely correlative. In this regard, further definition of regulatory pathways and directed gene ablation studies would be helpful in defining the respective roles of these factors in controlling vessel architecture in development and disease.

	Acknowledgments

 
This work was supported by National Institutes of Health Grants RO1-HL50692, RO1-AG15052, RO1-AR40197 and PO1-HD23681. We thank Linda Whittaker for aid in preparing this manuscript.

Received April 14, 2000; accepted June 12, 2000.

	References

Top Introduction Vascular Cell Apoptosis During... Apoptosis in Chronic Vascular... Vascular Cell Apoptosis Induced... Regulation of Vascular Cell... Death Receptor/Ligand... Closing Remarks References

 
1. Slomp J, Gittenberger-de Groot AC, Glukhova MA, van Musteren C, Kockx MM, Schwarz SM, Koteliansky VE. Differentiation, dedifferentiation, and apoptosis of smooth muscle cells during the development of the human ductus arteriosus. Arterioscler Thromb Vasc Biol. 1997;17:1003–1009.[Abstract/Free Full Text]

2. Kim HS, Hwang KK, Seo JW, Kim SY, Oh BH, Lee MM, Park YB. Apoptosis and regulation of Bax and Bcl-X proteins during human neonatal vascular remodeling. Arterioscler Thromb Vasc Biol. 2000;20:957–963.[Abstract/Free Full Text]

3. Cho A, Courtman DW, Langille BL. Apoptosis (programmed cell death) in arteries of the neonatal lamb. Circ Res. 1995;76:168–175.[Abstract/Free Full Text]

4. Cho A, Mitchell L, Koopmans D, Langille BL. Effects of changes in blood flow rate on cell death and cell proliferation in carotid arteries of immature rabbits. Circ Res. 1997;81:328–337.[Abstract/Free Full Text]

5. Bayer IM, Adamson SL, Langille BL. Atrophic remodeling of the artery-cuffed artery. Arterioscler Thromb Vasc Biol. 1999;19:1499–1505.[Abstract/Free Full Text]

6. Lauth M, Berger MM, Cattaruzza M, Hecker M. Elevated perfusion pressure upregulates endothelin-1 and endothelin B receptor expression in the rabbit carotid artery. Hypertension. 2000;35:648–654.[Abstract/Free Full Text]

7. Jones PL, Crack J, Rabinovitch M. Regulation of tenascin-C, a vascular smooth muscle cell survival factor that interacts with the _vß₃ integrin to promote epidermal growth factor receptor phosphorylation and growth. J Cell Biol. 1997;139:279–293.[Abstract/Free Full Text]

8. Baker AH, Zaltsman AB, George SJ, Newby AC. Divergent effects of tissue inhibitor of metalloproteinase-1, -2, -3 overexpression on rat vascular smooth muscle cell invasion, proliferation and death in vitro. TIMP-3 promotes apoptosis. J Clin Invest. 1998;101:1478–1487.[Medline] [Order article via Infotrieve]

9. Bennett 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.

10. Geng JY, Libby P. Evidence for apoptosis in advanced human atheroma: colocalization with interleukin-1ß converting enzyme. Am J Pathol. 1995;147:251–266.[Abstract]

11. Isner JM, Kearney M, Bortman S, Passeri J. Apoptosis in human atherosclerosis and restenosis. Circulation. 1995;91:2703–2711.[Abstract/Free Full Text]

12. Mallat Z, Ohan J, Leseche G, Tedugi A. Colocalization of CPP-32 with apoptotic cells in human atherosclerotic plaques. Circulation. 1997;96:424–428.[Abstract/Free Full Text]

13. Bjorkerud S, Bjorkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol. 1996;149:367–380.[Abstract]

14. Kockx MM, De Meyer GR, Muhring J, Jacob W, Bult H, Herman AG. Apoptosis and related proteins in different stages of human atherosclerotic plaques. Circulation. 1998;97:2307–2315.[Abstract/Free Full Text]

15. Kearney M, Pieczek A, Haley L, Losordo DW, Andrés V, Schainfeld R, Rosenfield K, Isner JM. Histopathology of in-stent restenosis in patients with peripheral artery disease. Circulation. 1997;95:1998–2002.[Abstract/Free Full Text]

16. Kockx MM, DeMeyer GRY, Muhring J, Bult H, Bultinck J, Herman AG. Distribution of cell replication and apoptosis in atherosclerotic plaques of cholesterol-fed rabbits. Atherosclerosis. 1996;120:115–124.[Medline] [Order article via Infotrieve]

17. Lutgens E, Daemen M, Kockx M, Doevendans P, Hofker M, Havekes I, Wellens H, de Muinck ED. Atherosclerosis in APOE*3-Leiden transgenic mice: from proliferative to atheromatous stage. Circulation. 1999;99:276–283.[Abstract/Free Full Text]

18. Harada K, Chen Z, Ishibashi S, Osuga J, Yagyu H, Ohashi K, Yahagi N, Shionoiri F, Sun L, Yazaki Y, Yamada N. Apoptotic cell death in atherosclerotic plaques of hyperlipidemic knockout mice. Atherosclerosis. 1997;135:235–239.[Medline] [Order article via Infotrieve]

19. Bennett MR, Macdonald K, Chan SW, Boyle JJ, Weissberg PL. Cooperative interactions between RB and p53 regulate cell proliferation, cell senescence, and apoptosis in human vascular smooth muscle cells from atherosclerotic plaques. Circ Res. 1998;82:704–712.[Abstract/Free Full Text]

20. Crisby M, Kallin B, Thyberg J, Zhivotovsky B, Orrenius S, Kostulas V, Nilsson J. Cell death in human atherosclerotic plaques involves both oncosis and apoptosis. Atherosclerosis. 1997;130:17–27.[Medline] [Order article via Infotrieve]

21. Perlman H, Maillard L, Krasinski K, Walsh K. Evidence for the rapid onset of apoptosis in medial smooth muscle cells following balloon injury. Circulation. 1997;95:981–987.[Abstract/Free Full Text]

22. Wei GL, Krasinski K, Kearney M, Isner JM, Walsh K, Andrés V. Temporally and spatially coordinated expression of cell cycle regulatory factors after angioplasty. Circ Res. 1997;80:418–426.

23. Miwa K, Asano M, Horai R, Iwakura Y, Nagata S, Suda T. Caspase 1-independent IL-1ß release and inflammation induced by the apoptosis inducer Fas ligand. Nat Med. 1998;4:1287–1292.[Medline] [Order article via Infotrieve]

24. Bochaton-Piallat M, Gabbiani F, Redard M, Desmouliere A, Gabbiani G. Apoptosis participates in cellularity regulation during rat aortic intimal thickening. Am J Pathol. 1995;146:1059–1064.[Abstract]

25. Han DKM, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol. 1995;147:267–277.[Abstract]

26. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury, I: smooth muscle cell growth in the absence of endothelium. Lab Invest. 1983;49:327–333.[Medline] [Order article via Infotrieve]

27. Rivard A, Luo Z, Perlman H, Fabre JE, Nguyen T, Maillard L, Walsh K. Early cell loss after angioplasty results in a disproportionate decrease in percutaneous gene transfer to the vessel wall. Hum Gene Ther. 1999;10:711–721.[Medline] [Order article via Infotrieve]

28. Pollman MJ, Hall JL, Gibbons GH. Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty injury. Circ Res. 1999;84:113–121.[Abstract/Free Full Text]

29. Pollman MJ, Hall ZL, Mann MJ, Zhang L, Gibbons GH. Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease. Nat Med. 1998;4:222–227.[Medline] [Order article via Infotrieve]

30. Song JM, Kim HS, Rhee MY, Chae IH, Sohn DW, Oh BH, Lee MM, Park YB, Choi YS, Lee YW. Effect of hypercholesterolemia on the sequential changes of apoptosis and proliferation after balloon injury to rabbit iliac artery. Atherosclerosis. 2000;150:309–320.[Medline] [Order article via Infotrieve]

31. Kollum M, Kaiser S, Kinscherf R, Metz J, Kubler W, Hehrlein C. Apoptosis after stent implantation compared with balloon angioplasty in rabbits. Role of macrophages. Arterioscler Thromb Vasc Biol. 1997;17:2382–2388.

32. Malik N, Francis SE, Holt CM, Gunn J, Thomas GL, Shepherd L, Chamberlain J, Newman CMH, Cumberland DC, Crossman DC. Apoptosis and cell proliferation after porcine coronary angioplasty. Circulation. 1998;98:1657–1665.[Abstract/Free Full Text]

33. Perlman H, Sata M, Krasinski K, Dorai T, Buttyan R, Walsh K. Adenovirus-encoded hammerhead ribozyme to Bcl-2 inhibits neointimal hyperplasia and induces smooth muscle cell apoptosis. Cardiovasc Res. 2000;45:570–578.[Abstract/Free Full Text]

34. Ihling C, Haendeler J, Menzel G, Hess RD, Fraedrich G, Schaefer HE, Zeiher AM. Co-expression of p53 and MDM2 in human atherosclerosis: implications for the regulation of cellularity of atherosclerotic lesions. J Pathol. 1998;185:303–312.[Medline] [Order article via Infotrieve]

35. Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995;80:293–299.[Medline] [Order article via Infotrieve]

36. Miyashita T, Harigal M, Hanada M, Reed JC. Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res. 1994;54:3131–3135.[Abstract/Free Full Text]

37. Bennett M, Macdonald K, Chan SW, Luzio JP, Simari R, Weissberg P. Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science. 1998;282:290–293.[Abstract/Free Full Text]

38. Yonemitsu Y, Kaneda Y, Tanaka S, Nakashima Y, Komori K, Sugimachi K, Sueishi K. Transfer of wild-type p53 gene effectively inhibits vascular smooth muscle cell proliferation in vitro and in vivo. Circ Res. 1998;82:147–156.[Abstract/Free Full Text]

39. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817–825.[Medline] [Order article via Infotrieve]

40. Guevara NV, Kim HS, Antonova EI, Chan L. The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo. Nat Med. 1999;5:335–339.[Medline] [Order article via Infotrieve]

41. Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, Nagata S. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994;76:969–976.[Medline] [Order article via Infotrieve]

42. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356:314–317.[Medline] [Order article via Infotrieve]

43. Nagata S, Golstein P. The Fas death factor. Science. 1995;267:1449–1456.[Abstract/Free Full Text]

44. Kiener PA, Davis PM, Starling GC, Mehlin C, Klebanoff SJ, Ledbetter JA, Liles WC. Differential induction of apoptosis by Fas-Fas ligand interactions in human monocytes and macrophages. J Exp Med. 1997;185:1511–1516.[Abstract/Free Full Text]

45. Kiener PA, Davis PM, Rankin BM, Klebanoff SJ, Ledbetter JA, Starling GC, Liles WC. Human monocytic cells contain high levels of intracellular Fas ligand: rapid release following cellular activation. J Immunol. 1997;159:1594–1598.[Abstract]

46. Perlman H, Pagliari LJ, Georganas C, Mano T, Walsh K, Pope RM. FLICE-inhibitory protein expression during macrophage differentiation confers resistance to Fas-mediated apoptosis. J Exp Med. 1999;190:1679–1688.[Abstract/Free Full Text]

47. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995;270:1189–1192.[Abstract/Free Full Text]

48. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC. A role of CD95 ligand in preventing graft rejection. Nature. 1995;377:630–632.[Medline] [Order article via Infotrieve]

49. Sata M, Walsh K. TNF regulation of Fas ligand expression on the vascular endothelium modulates leukocyte extravasation. Nat Med. 1998;4:415–420.[Medline] [Order article via Infotrieve]

50. Sata M, Suhara T, Walsh K. Vascular endothelial cells and smooth muscle cells differ in their expression of Fas and Fas ligand and in their sensitivity to Fas ligand-induced cell death: implications for vascular disease and therapy. Arterioscler Thromb Vasc Biol. 2000;20:309–316.[Abstract/Free Full Text]

51. Sata M, Walsh K. Oxidized LDL activates Fas-mediated endothelial cell apoptosis. J Clin Invest. 1998;102:1682–1689.[Medline] [Order article via Infotrieve]

52. Fukuo K, Nakahashi T, Nomura S, Hata S, Suhara T, Shimizu M, Tamatani M, Morimoto S, Kitamura Y, Ogihara T. Possible participation of Fas-mediated apoptosis in the mechanism of atherosclerosis. Gerontology. 1997;43:35–42.

53. Cai W, Devaux B, Schaper W, Schaper J. The role of Fas/APO 1 and apoptosis in the development of human atherosclerotic lesions. Atherosclerosis. 1997;131:177–186.[Medline] [Order article via Infotrieve]

54. Geng Y-J, Henderson LE, Levesque EB, Muszynzki M, Libby P. Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1997;17:2200–2208.[Abstract/Free Full Text]

55. Schneider DB, Vassalli G, Wen S, Driscoll RM, Sassani AB, DeYoung MB, Linnemann R, Virmani R, Dichek DA. Expression of Fas ligand in arteries of hypercholesterolemic rabbits accelerates atherosclerotic lesion formation. Arterioscler Thromb Vasc Biol. 2000;20:298–308.[Abstract/Free Full Text]

56. Dong C, Wilson JE, Winters GL, McManus BM. Human transplant coronary artery disease: pathological evidence for Fas-mediated apoptotic cytotoxicity in allograft arteriopathy. Lab Invest. 1996;74:921–931.[Medline] [Order article via Infotrieve]

57. Sata M, Perlman H, Muruve DA, Silver M, Ikebe M, Libermann TA, Oettgen P, Walsh K. Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response. Proc Natl Acad Sci U S A. 1998;95:1213–1217.[Abstract/Free Full Text]

58. Tanaka M, Itai T, Adachi M, Nagata S. Downregulation of Fas ligand by shedding. Nat Med. 1998;4:31–36.[Medline] [Order article via Infotrieve]

59. Fukuo K, Suhara T, Nakahashi T, Hata S, Shimizu M, Niinobu T, Morimoto S, Ogihara T. Activated T cells induce up-regulation of Fas antigen in cultured endothelial cells. Heart Vessels. 1997;suppl 12:81–83.

60. Richardson BC, Lalwani ND, Johnson KJ, Marks RM. Fas ligation triggers apoptosis in macrophages but not endothelial cells. Eur J Immunol. 1994;24:2640–2645.[Medline] [Order article via Infotrieve]

61. Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer J-L, Schroter M, Burns K, Mattmann C, Rimoldi D, French L, Tschopp J. Inhibition of death receptor signals by cellular FLIP. Nature. 1997;388:190–195.[Medline] [Order article via Infotrieve]

62. Han DKM, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM, Hood L. MRIT, a novel death-effector domain-containing protein, interacts with caspases and Bcl_XL and initiates cell death. Proc Natl Acad Sci U S A. 1997;94:11333–11338.[Abstract/Free Full Text]

63. Sata M, Walsh K. Endothelial cell apoptosis induced by oxidized LDL is associated with the downregulation of the cellular caspase inhibitor FLIP. J Biol Chem. 1998;273:33103–33106.[Abstract/Free Full Text]

64. Imanishi T, McBride J, Ho Q, O’Brien KD, Schwartz SM, Han DKM. Expression of cellular FLICE-inhibitor protein in human coronary arteries and in a rat vascular injury model. Am J Pathol. 2000;156:125–137.[Abstract/Free Full Text]

65. Hewicker M, Trautwein G. Sequential study of vasculitis in MRL mice. Lab Anim. 1987;21:335–341.[Abstract/Free Full Text]

66. Taniguchi Y, Ito MR, Mori S, Yonehara S, Nose M. Role of macrophages in the development of arteritis in MRL strains of mice with a deficit in Fas-mediated apoptosis. Clin Exp Immunol. 1996;106:26–34.[Medline] [Order article via Infotrieve]

67. Sata M, Walsh K. Fas ligand-deficient mice display enhanced leukocyte infiltration and intima hyperplasia in flow-restricted vessels. J Mol Cell Cardiol. In press.

68. Luo Z, Sata M, Nguyen T, Kaplan JM, Akita GY, Walsh K. Adenovirus-mediated delivery of Fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals. Circulation. 1999;99:1776–1779.[Abstract/Free Full Text]

This article has been cited by other articles:

				I. E. Dumitriu, E. T. Araguas, C. Baboonian, and J. C. Kaski CD4+CD28null T cells in coronary artery disease: when helpers become killers Cardiovasc Res, January 1, 2009; 81(1): 11 - 19. [Abstract] [Full Text] [PDF]

				M. K. Reddy, J. K. Vasir, S. K. Sahoo, T. K. Jain, M. M. Yallapu, and V. Labhasetwar Inhibition of Apoptosis Through Localized Delivery of Rapamycin-Loaded Nanoparticles Prevented Neointimal Hyperplasia and Reendothelialized Injured Artery Circ Cardiovasc Interv, December 1, 2008; 1(3): 209 - 216. [Abstract] [Full Text] [PDF]

				A. Schober Chemokines in Vascular Dysfunction and Remodeling Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1950 - 1959. [Abstract] [Full Text] [PDF]

				S. Kondo, Y. Tang, E. A. Scheef, N. Sheibani, and C. M. Sorenson Attenuation of retinal endothelial cell migration and capillary morphogenesis in the absence of bcl-2 Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1521 - C1530. [Abstract] [Full Text] [PDF]

				D. G. Sedding, M. Homann, U. Seay, H. Tillmanns, K. T. Preissner, and R. C. Braun-Dullaeus Calpain counteracts mechanosensitive apoptosis of vascular smooth muscle cells in vitro and in vivo FASEB J, February 1, 2008; 22(2): 579 - 589. [Abstract] [Full Text] [PDF]

				S. M. Sanz-Gonzalez, L. Barquin, I. Garcia-Cao, M. Roque, J. M. Gonzalez, J. J. Fuster, M. T. Castells, J. M. Flores, M. Serrano, and V. Andres Increased p53 gene dosage reduces neointimal thickening induced by mechanical injury but has no effect on native atherosclerosis Cardiovasc Res, September 1, 2007; 75(4): 803 - 812. [Abstract] [Full Text] [PDF]

				R. Chen, L. Yang, and T. M. McIntyre Cytotoxic Phospholipid Oxidation Products: CELL DEATH FROM MITOCHONDRIAL DAMAGE AND THE INTRINSIC CASPASE CASCADE J. Biol. Chem., August 24, 2007; 282(34): 24842 - 24850. [Abstract] [Full Text] [PDF]

				M. Aikawa The Balance of Power: The Law of Yin and Yang in Smooth Muscle Cell Fate: Is YY1 a Vascular Protector? Circ. Res., July 20, 2007; 101(2): 111 - 113. [Full Text] [PDF]

				A.-L. Levonen, M. Inkala, T. Heikura, S. Jauhiainen, H.-K. Jyrkkanen, E. Kansanen, K. Maatta, E. Romppanen, P. Turunen, J. Rutanen, et al. Nrf2 Gene Transfer Induces Antioxidant Enzymes and Suppresses Smooth Muscle Cell Growth In Vitro and Reduces Oxidative Stress in Rabbit Aorta In Vivo Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 741 - 747. [Abstract] [Full Text] [PDF]

				C.-H. Wang, S. Verma, I-C. Hsieh, A. Hung, T.-T. Cheng, S.-Y. Wang, Y.-C. Liu, W. L. Stanford, R. D. Weisel, R.-K. Li, et al. Stem Cell Factor Attenuates Vascular Smooth Muscle Apoptosis and Increases Intimal Hyperplasia After Vascular Injury Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 540 - 547. [Abstract] [Full Text] [PDF]

				A. Orlandi, A. Francesconi, M. Marcellini, A. Di Lascio, and L. G. Spagnoli Propionyl-L-carnitine Reduces Proliferation and Potentiates Bax-related Apoptosis of Aortic Intimal Smooth Muscle Cells by Modulating Nuclear Factor-{kappa}B Activity J. Biol. Chem., February 16, 2007; 282(7): 4932 - 4942. [Abstract] [Full Text] [PDF]

				S. Isobe, S. Tsimikas, J. Zhou, S. Fujimoto, M. Sarai, M. J. Branks, A. Fujimoto, L. Hofstra, C. P. Reutelingsperger, T. Murohara, et al. Noninvasive Imaging of Atherosclerotic Lesions in Apolipoprotein E-Deficient and Low-Density-Lipoprotein Receptor-Deficient Mice with Annexin A5 J. Nucl. Med., September 1, 2006; 47(9): 1497 - 1505. [Abstract] [Full Text] [PDF]

				K. R. Brunt, K. K. Fenrich, G. Kiani, M. Yat Tse, S. C. Pang, C. A. Ward, and L. G. Melo Protection of Human Vascular Smooth Muscle Cells From H2O2-Induced Apoptosis Through Functional Codependence Between HO-1 and AKT Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 2027 - 2034. [Abstract] [Full Text] [PDF]

				J. L. Martin-Ventura, V. Nicolas, X. Houard, L. M. Blanco-Colio, A. Leclercq, J. Egido, R. Vranckx, J.-B. Michel, and O. Meilhac Biological Significance of Decreased HSP27 in Human Atherosclerosis Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1337 - 1343. [Abstract] [Full Text] [PDF]

				C. A. Pfrommer, W. Erl, and P. C. Weber Docosahexaenoic acid induces ciap1 mRNA and protects human endothelial cells from stress-induced apoptosis Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2178 - H2186. [Abstract] [Full Text] [PDF]

				S. Lim, C. J. Jin, M. Kim, S. S. Chung, H. S. Park, I. K. Lee, C. T. Lee, Y. M. Cho, H. K. Lee, and K. S. Park PPAR{gamma} Gene Transfer Sustains Apoptosis, Inhibits Vascular Smooth Muscle Cell Proliferation, and Reduces Neointima Formation After Balloon Injury in Rats Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 808 - 813. [Abstract] [Full Text] [PDF]

				H. Ono, T. Ichiki, H. Ohtsubo, K. Fukuyama, I. Imayama, Y. Hashiguchi, J. Sadoshima, and K. Sunagawa Critical Role of Mst1 in Vascular Remodeling After Injury Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1871 - 1876. [Abstract] [Full Text] [PDF]

				A. Zernecke, A. Schober, I. Bot, P. von Hundelshausen, E. A. Liehn, B. Mopps, M. Mericskay, P. Gierschik, E. A. Biessen, and C. Weber SDF-1{alpha}/CXCR4 Axis Is Instrumental in Neointimal Hyperplasia and Recruitment of Smooth Muscle Progenitor Cells Circ. Res., April 15, 2005; 96(7): 784 - 791. [Abstract] [Full Text] [PDF]

				S. V. Ashton, G. St. J. Whitley, P. R. Dash, M. Wareing, I. P. Crocker, P. N. Baker, and J. E. Cartwright Uterine Spiral Artery Remodeling Involves Endothelial Apoptosis Induced by Extravillous Trophoblasts Through Fas/FasL Interactions Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 102 - 108. [Abstract] [Full Text] [PDF]

				W. Wang, W. Sun, and X. Wang Intramuscular gene transfer of CGRP inhibits neointimal hyperplasia after balloon injury in the rat abdominal aorta Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1582 - H1589. [Abstract] [Full Text] [PDF]

				M. L. Rossi, N. Marziliano, P. A. Merlini, E. Bramucci, U. Canosi, G. Belli, D. Z. Parenti, P. M. Mannucci, and D. Ardissino Different Quantitative Apoptotic Traits in Coronary Atherosclerotic Plaques From Patients With Stable Angina Pectoris and Acute Coronary Syndromes Circulation, September 28, 2004; 110(13): 1767 - 1773. [Abstract] [Full Text] [PDF]

				J. Yang, K. Sato, T. Aprahamian, N. J. Brown, J. Hutcheson, A. Bialik, H. Perlman, and K. Walsh Endothelial Overexpression of Fas Ligand Decreases Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1466 - 1473. [Abstract] [Full Text] [PDF]

				D. Nagata, R. Takeda, M. Sata, H. Satonaka, E. Suzuki, T. Nagano, and Y. Hirata AMP-Activated Protein Kinase Inhibits Angiotensin II-Stimulated Vascular Smooth Muscle Cell Proliferation Circulation, July 27, 2004; 110(4): 444 - 451. [Abstract] [Full Text] [PDF]

				T. Aprahamian, I. Rifkin, R. Bonegio, B. Hugel, J.-M. Freyssinet, K. Sato, J. J. Castellot Jr., and K. Walsh Impaired Clearance of Apoptotic Cells Promotes Synergy between Atherogenesis and Autoimmune Disease J. Exp. Med., April 19, 2004; 199(8): 1121 - 1131. [Abstract] [Full Text] [PDF]

				C. Skurk, H. Maatz, H.-S. Kim, J. Yang, M. R. Abid, W. C. Aird, and K. Walsh The Akt-regulated Forkhead Transcription Factor FOXO3a Controls Endothelial Cell Viability through Modulation of the Caspase-8 Inhibitor FLIP J. Biol. Chem., January 9, 2004; 279(2): 1513 - 1525. [Abstract] [Full Text] [PDF]

				J.-B. Michel Anoikis in the Cardiovascular System: Known and Unknown Extracellular Mediators Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2146 - 2154. [Abstract] [Full Text] [PDF]

				T. C. Tung, G. Cui, K. Oshima, H. Laks, and L. Sen Balanced expression of mitochondrial apoptosis regulatory proteins correlates with long-term survival of cardiac allografts Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2832 - H2841. [Abstract] [Full Text] [PDF]

				T. Tokunou, R. Shibata, H. Kai, T. Ichiki, T. Morisaki, K. Fukuyama, H. Ono, N. Iino, S. Masuda, H. Shimokawa, et al. Apoptosis Induced by Inhibition of Cyclic AMP Response Element-Binding Protein in Vascular Smooth Muscle Cells Circulation, September 9, 2003; 108(10): 1246 - 1252. [Abstract] [Full Text] [PDF]

				M. Sata, K. Tanaka, N. Ishizaka, Y. Hirata, and R. Nagai Absence of p53 Leads to Accelerated Neointimal Hyperplasia After Vascular Injury Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1548 - 1552. [Abstract] [Full Text] [PDF]

				K.-W. Park, H.-M. Yang, S.-W. Youn, H.-J. Yang, I.-H. Chae, B.-H. Oh, M.-M. Lee, Y.-B. Park, Y.-S. Choi, H.-S. Kim, et al. Constitutively Active Glycogen Synthase Kinase-3{beta} Gene Transfer Sustains Apoptosis, Inhibits Proliferation of Vascular Smooth Muscle Cells, and Reduces Neointima Formation After Balloon Injury in Rats Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1364 - 1369. [Abstract] [Full Text] [PDF]

				C. Napoli, L. O. Lerman, F. de Nigris, J. Loscalzo, and L. J. Ignarro Glycoxidized low-density lipoprotein downregulates endothelial nitricoxide synthase in human coronary cells J. Am. Coll. Cardiol., October 16, 2002; 40(8): 1515 - 1522. [Abstract] [Full Text] [PDF]

				M. O. Laukkanen, A. Kivela, T. Rissanen, J. Rutanen, M. K. Karkkainen, O. Leppanen, J. H. Brasen, and S. Yla-Herttuala Adenovirus-Mediated Extracellular Superoxide Dismutase Gene Therapy Reduces Neointima Formation in Balloon-Denuded Rabbit Aorta Circulation, October 8, 2002; 106(15): 1999 - 2003. [Abstract] [Full Text] [PDF]

				R. Kraemer Reduced Apoptosis and Increased Lesion Development in the Flow-Restricted Carotid Artery of p75NTR-Null Mutant Mice Circ. Res., September 20, 2002; 91(6): 494 - 500. [Abstract] [Full Text] [PDF]

				T. Nakajima, S. Schulte, K. J. Warrington, S. L. Kopecky, R. L. Frye, J. J. Goronzy, and C. M. Weyand T-Cell-Mediated Lysis of Endothelial Cells in Acute Coronary Syndromes Circulation, February 5, 2002; 105(5): 570 - 575. [Abstract] [Full Text] [PDF]

				T. Suhara, H.-S. Kim, L. A. Kirshenbaum, and K. Walsh Suppression of Akt Signaling Induces Fas Ligand Expression: Involvement of Caspase and Jun Kinase Activation in Akt-Mediated Fas Ligand Regulation Mol. Cell. Biol., January 15, 2002; 22(2): 680 - 691. [Abstract] [Full Text] [PDF]

				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]

				M. Sata, S. Sugiura, M. Yoshizumi, Y. Ouchi, Y. Hirata, and R. Nagai Acute and Chronic Smooth Muscle Cell Apoptosis After Mechanical Vascular Injury Can Occur Independently of the Fas-Death Pathway Arterioscler Thromb Vasc Biol, November 1, 2001; 21(11): 1733 - 1737. [Abstract] [Full Text] [PDF]

				C. Patterson, G. A. Stouffer, N. Madamanchi, and M. S. Runge New Tricks for Old Dogs : Nonthrombotic Effects of Thrombin in Vessel Wall Biology Circ. Res., May 25, 2001; 88(10): 987 - 997. [Abstract] [Full Text] [PDF]

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walsh, K. Articles by Kim, H.-S. Search for Related Content PubMed PubMed Citation Articles by Walsh, K. Articles by Kim, H.-S. Related Collections Animal models of human disease Apoptosis Gene regulation Other arteriosclerosis Other Vascular biology