ROLE OF TRANSFORMING GROWTH-FACTOR-BETA-1 IN THE CELLULAR GROWTH-RESPONSE TO ANGIOTENSIN-II

被引:88
作者
KOIBUCHI, Y [1 ]
LEE, WS [1 ]
GIBBONS, GH [1 ]
PRATT, RE [1 ]
机构
[1] STANFORD UNIV, MED CTR,SCH MED,FALK CARDIOVASC RES CTR, DIV CARDIOVASC MED,300 PASTEUR DR, STANFORD, CA 94305 USA
关键词
TRANSFORMING GROWTH FACTORS; HYPERPLASIA; HYPERTROPHY; MUSCLE; SMOOTH; VASCULAR; ANGIOTENSIN-II; FIBROBLAST GROWTH FACTOR;
D O I
10.1161/01.HYP.21.6.1046
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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-beta1 (TGF-beta1), respectively. We now present evidence, based on two phenotypically distinct cell cultures, that the ability to secrete the biologically active form of TGF-beta1 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-beta1. In the culture that responds with hypertrophy, Ang II induces the expression of the active form of TGF-beta1 twofold to threefold. However, in the culture that responds with hyperplasia, no active TGF-beta1 was detected either at baseline or after Ang II exposure. Interestingly, all the TGF-beta1 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-beta1. Thus in these two cultures the ability to activate TGF-beta1 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.
引用
收藏
页码:1046 / 1050
页数:5
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