ANG II Induces Apoptosis of Human Vascular Smooth Muscle Via Extrinsic Pathway Involving Inhibition of Akt Phosphorylation and Increased FasL Expression

Overview

Journal Am J Physiol Heart Circ Physiol

Publisher American Physiological Society

Specialties Cardiology & Vascular Diseases
Physiology

Date 2005 Dec 13

PMID 16339840

Citations 15

Authors

Yangxin Li

Yao-Hua Song

Jessica Mohler

Patrick Delafontaine

Affiliations

Soon will be listed here.

Abstract

In addition to well-documented vascular growth-promoting effects, ANG II exerts proapoptotic effects that are poorly understood. IGF-1 is a potent survival factor for human vascular smooth muscle cells (hVSMC), and its antiapoptotic effects are mediated via the IGF-1 receptor (IGF-1R) through a signaling pathway involving phosphatidylinositol 3-kinase and Akt. We hypothesized that there would be cross talk between ANG II proapoptotic effects and IGF-1 survival effects in hVSMC. To investigate ANG II-induced apoptosis and the potential involvement of IGF-1, we exposed quiescent and nonquiescent hVSMC to ANG II. ANG II induced apoptosis only in nonquiescent cells but stimulated hypertrophy in quiescent cells. ANG II-induced apoptosis was characterized by marked inhibition of Akt phosphorylation and stimulation of membrane Fas ligand (FasL) expression, caspase-8 activation, and a reduction in soluble FasL expression. Adenovirally mediated overexpression of Akt rescued hVSMC from ANG II-induced apoptosis. IGF-1R activation increased Akt phosphorylation and soluble FasL expression, and these effects were completely blocked by coincubating hVSMC with ANG II. In conclusion, ANG II-induced apoptosis of hVSMC is characterized by marked inhibition of Akt phosphorylation and stimulation of an extrinsic cell death signaling pathway via upregulation of membrane FasL expression, caspase-8 activation, and a reduction in soluble FasL expression. Furthermore, ANG II antagonizes the antiapoptotic effect of IGF-1 by blocking its ability to increase Akt phosphorylation and soluble FasL. These findings provide novel insights into ANG II-induced apoptotic signaling and have significant implication for understanding ANG II-induced remodeling in hypertension and atherosclerosis.

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References

Babaev V, Bobryshev Y, Stenina O, Tararak E, Gabbiani G . Heterogeneity of smooth muscle cells in atheromatous plaque of human aorta. Am J Pathol. 1990; 136(5):1031-42. PMC: 1877438. View

Geisterfer A, Peach M, Owens G . Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res. 1988; 62(4):749-56. DOI: 10.1161/01.res.62.4.749. View

Ross R . The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362(6423):801-9. DOI: 10.1038/362801a0. View

Weber H, Taylor D, Molloy C . Angiotensin II induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin. J Clin Invest. 1994; 93(2):788-98. PMC: 293930. DOI: 10.1172/JCI117033. View

Nagata S, Golstein P . The Fas death factor. Science. 1995; 267(5203):1449-56. DOI: 10.1126/science.7533326. View

Feener E, Northrup J, Aiello L, King G . Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells. J Clin Invest. 1995; 95(3):1353-62. PMC: 441475. DOI: 10.1172/JCI117786. View

Yamada T, Horiuchi M, Dzau V . Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci U S A. 1996; 93(1):156-60. PMC: 40197. DOI: 10.1073/pnas.93.1.156. View

Fukuo K, Hata S, Suhara T, Nakahashi T, Shinto Y, Tsujimoto Y . Nitric oxide induces upregulation of Fas and apoptosis in vascular smooth muscle. Hypertension. 1996; 27(3 Pt 2):823-6. DOI: 10.1161/01.hyp.27.3.823. View

Velloso L, Folli F, Sun X, White M, Saad M, Kahn C . Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci U S A. 1996; 93(22):12490-5. PMC: 38019. DOI: 10.1073/pnas.93.22.12490. View

10.

Diet F, PRATT R, Berry G, Momose N, Gibbons G, Dzau V . Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease. Circulation. 1996; 94(11):2756-67. DOI: 10.1161/01.cir.94.11.2756. View

11.

Nagata S . Apoptosis by death factor. Cell. 1997; 88(3):355-65. DOI: 10.1016/s0092-8674(00)81874-7. View

12.

Dore S, Kar S, Quirion R . Insulin-like growth factor I protects and rescues hippocampal neurons against beta-amyloid- and human amylin-induced toxicity. Proc Natl Acad Sci U S A. 1997; 94(9):4772-7. PMC: 20800. DOI: 10.1073/pnas.94.9.4772. View

13.

Horiuchi M, Yamada T, Hayashida W, Dzau V . Interferon regulatory factor-1 up-regulates angiotensin II type 2 receptor and induces apoptosis. J Biol Chem. 1997; 272(18):11952-8. DOI: 10.1074/jbc.272.18.11952. View

14.

Bennett M, Littlewood T, Schwartz S, Weissberg P . Increased sensitivity of human vascular smooth muscle cells from atherosclerotic plaques to p53-mediated apoptosis. Circ Res. 1997; 81(4):591-9. DOI: 10.1161/01.res.81.4.591. View

15.

Geng Y, Henderson L, Levesque E, Muszynski 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(10):2200-8. DOI: 10.1161/01.atv.17.10.2200. View

16.

Folli F, Kahn C, Hansen H, Bouchie J, Feener E . Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. J Clin Invest. 1997; 100(9):2158-69. PMC: 508410. DOI: 10.1172/JCI119752. View

17.

Suda T, Hashimoto H, Tanaka M, Ochi T, Nagata S . Membrane Fas ligand kills human peripheral blood T lymphocytes, and soluble Fas ligand blocks the killing. J Exp Med. 1998; 186(12):2045-50. PMC: 2199173. DOI: 10.1084/jem.186.12.2045. View

18.

Frid M, Aldashev A, Dempsey E, Stenmark K . Smooth muscle cells isolated from discrete compartments of the mature vascular media exhibit unique phenotypes and distinct growth capabilities. Circ Res. 1997; 81(6):940-52. DOI: 10.1161/01.res.81.6.940. View

19.

Tanaka M, ITAI T, Adachi M, Nagata S . Downregulation of Fas ligand by shedding. Nat Med. 1998; 4(1):31-6. DOI: 10.1038/nm0198-031. View

20.

Haunstetter A, Izumo S . Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ Res. 1998; 82(11):1111-29. DOI: 10.1161/01.res.82.11.1111. View