Role of transforming growth factor-beta 1 in the cellular growth response to angiotensin II.

We have shown that angiotensin II (Ang II)-induced hypertrophy of vascular smooth muscle cells is dependent on the balance between proliferative and antiproliferative growth factors, specifically basic fibroblast growth factor and transforming growth factor-beta 1 (TGF-beta 1), respectively. We now present evidence, based on two phenotypically distinct cell cultures, that the ability to secrete the biologically active form of TGF-beta 1 is central to the growth response to Ang II. Two separate cultures were examined, one in which Ang II induces hypertrophy and the other in which Ang II induces hyperplasia. Ang II induces the expression of basic fibroblast growth factor twofold to fivefold in both cultures. Furthermore, both cultures express TGF-beta 1. In the culture that responds with hypertrophy, Ang II induces the expression of the active form of TGF-beta 1 twofold to threefold. However, in the culture that responds with hyperplasia, no active TGF-beta 1 was detected either at baseline or after Ang II exposure. Interestingly, all the TGF-beta 1 present was in the inactive, latent form. In the culture that responded with hyperplasia, Ang II induced a fourfold to fivefold increase in DNA synthesis. This increase could be abolished by the addition of active TGF-beta 1. Thus in these two cultures the ability to activate TGF-beta 1 dictates the cellular response to Ang II. These results support our hypothesis that a balance of proliferative and antiproliferative autocrine signals mediates the growth control of vascular smooth muscle cells.

[1]  H. Itoh,et al.  Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II. , 1993, The Journal of clinical investigation.

[2]  G. Gibbons,et al.  Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II. , 1992, The Journal of clinical investigation.

[3]  H. Baumgartner,et al.  Role of Angiotensin II in Injury‐Induced Neointima Formation in Rats , 1991, Hypertension.

[4]  A. Chobanian,et al.  The effects of ACE inhibitors and other antihypertensive drugs on cardiovascular risk factors and atherogenesis , 1990, Clinical cardiology.

[5]  G. Åberg,et al.  Effects of Captopril on Atherosclerosis in Cynomolgus Monkeys , 1990, Journal of cardiovascular pharmacology.

[6]  Sandra R. Smith,et al.  An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[7]  V. Dzau,et al.  Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. , 1989, The Journal of clinical investigation.

[8]  M. Sporn,et al.  Immunodetection and quantitation of the two forms of transforming growth factor‐beta (TGF‐β1 and TGF‐β2) secreted by cells in culture , 1989 .

[9]  F. Lyall,et al.  Angiotensin II activates Na+-H+ exchange and stimulates growth in cultured vascular smooth muscle cells , 1988, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[10]  A. A. Geisterfer,et al.  Transforming growth factor-beta-induced growth inhibition and cellular hypertrophy in cultured vascular smooth muscle cells , 1988, The Journal of cell biology.

[11]  H. Moses,et al.  Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium , 1988, The Journal of cell biology.

[12]  D. Hajjar,et al.  Aging and arteriosclerosis. Cell cycle kinetics of young and old arterial smooth muscle cells. , 1988, The American journal of pathology.

[13]  J. Fiddes,et al.  Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth , 1987, Nature.

[14]  D. Hajjar,et al.  Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury , 1986, The Journal of experimental medicine.

[15]  M. Klagsbrun,et al.  Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Ross.  The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.

[17]  G. Owens,et al.  Expression of smooth muscle-specific alpha-isoactin in cultured vascular smooth muscle cells: relationship between growth and cytodifferentiation , 1986, The Journal of cell biology.

[18]  M. Reidy,et al.  Mechanisms of stenosis after arterial injury. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[19]  P. Libby,et al.  Culture of quiescent arterial smooth muscle cells in a defined serum‐free medium , 1983, Journal of cellular physiology.

[20]  J. Rowe,et al.  Vascular smooth muscle cell growth kinetics in vivo in aged rats. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Campbell-Boswell,et al.  Effects of angiotensin II and vasopressin on human smooth muscle cells in vitro. , 1981, Experimental and molecular pathology.

[22]  M. Mulvany,et al.  Direct Evidence that the Greater Contractility of Resistance Vessels in Spontaneously Hypertensive Rats is Associated with a Narrowed Lumen, a Thickened Media, and an Increased Number of Smooth Muscle Cell Layers , 1978, Circulation research.