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| MULTIPLE AUTOCRINE GROWTH-FACTORS MODULATE VASCULAR SMOOTH-MUSCLE CELL-GROWTH RESPONSE TO ANGIOTENSIN-II |
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| Author(s): ITOH H, MUKOYAMA M, PRATT RE, GIBBONS GH, DZAU VJ |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 91 Issue: 5 Pages: 2268-2274 Published: MAY 1993 |
| Times Cited: 387 References: 39 |
| Abstract: Angiotensin (Ang) II stimulates hypertrophic growth of vascular smooth muscle cells (VSMC). Accompanying this growth is the induction of the expression of growth-related protooncogenes (c-fos, c-jun, and c-myc), as well as the synthesis of the autocrine growth factors, such as PDGF-A and TGF-beta1. In this study, we demonstrate further that Ang II also induces the synthesis of basic fibroblast growth factor (bFGF), a potent mitogen for VSMC. To examine how these factors interact to modulate the growth response of VSMC to Ang II, we used antisense oligomers to determine the relative contribution of these three factors. Treatment of confluent, quiescent smooth muscle cells with specific antisense oligomers complementary to bFGF, PDGF-A, and TGF-beta1 efficiently inhibited the syntheses of these factors. Our results demonstrate that in these VSMC, TGF-beta1 affects a key antiproliferative action, modulating the mitogenic properties of bFGF. Autocrine PDGF exerts only a minimal effect on DNA synthesis. An imbalance in these signals activated by Ang II may result in abnormal VSMC growth leading to the development of vascular disease. |
| Document Type: Note |
| Language: English |
Addresses:
1. STANFORD UNIV, MED CTR, SCH MED, FALK CARDIOVASC RES CTR, DIV CARDIOVASC MED, 300 PASTEUR DR, STANFORD, CA 94305 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: LA726 |
| ISSN: 0021-9738 |
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