PMID- 8576949 OWN - NLM STAT- MEDLINE DCOM- 19960313 LR - 20190830 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 27 IP - 10 DP - 1995 Oct TI - Angiotensin II stimulates the autocrine production of transforming growth factor-beta 1 in adult rat cardiac fibroblasts. PG - 2347-57 AB - Angiotensin II (Ang II) has been implicated in the development of cardiac hypertrophy and myocardial fibrosis. While recent in vivo and in vitro studies performed in cultured cardiac myocytes and fibroblasts support this role for Ang II, the mechanisms of Ang II action at the cellular level remain unclear. In the present study, we postulated that Ang II action in adult cardiac fibroblasts may stimulate the autocrine production and release of transforming growth factor-beta 1 (TGF-beta 1), a known regulator of cardiac fibroblast and myocyte function. We examined the ability of Ang II to regulate the gene expression, biological activity, and protein production of TGF-beta 1 in cultured adult rat cardiac fibroblasts. Treatment of fibroblast cultures with Ang II (10(-9) M) induced a two-fold increase in TGF-beta 1 mRNA levels within 4 h that was sustained through 24 h (P < 0.01). TGF-beta 1-like activity in Ang II-treated cultures was significantly increased compared with control as measured by bioassay (P < 0.001). Specificity for TGF-beta 1-like activity was confirmed through its neutralization with a TGF-beta 1 specific antibody (100 micrograms/ml). Total concentration of TGF-beta 1 (latent plus active forms) in conditioned media from Ang II-treated cardiac fibroblasts was also found to be greater than control (P < 0.01). These findings suggest that the effects of Ang II in the adult myocardium may be mediated in part by autocrine/paracrine mechanisms, including the production and release of TGF-beta 1 by cardiac fibroblasts. FAU - Lee, A A AU - Lee AA AD - Department of Bioengineering, University of California, San Diego 92103, USA. FAU - Dillmann, W H AU - Dillmann WH FAU - McCulloch, A D AU - McCulloch AD FAU - Villarreal, F J AU - Villarreal FJ LA - eng GR - HL-43617/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Culture Media, Conditioned) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 11128-99-7 (Angiotensin II) SB - IM MH - Angiotensin II/*pharmacology MH - Animals MH - Cardiomegaly/metabolism MH - Culture Media, Conditioned/chemistry MH - Endomyocardial Fibrosis/metabolism MH - Fibroblasts/*drug effects/metabolism MH - Gene Expression Regulation/*drug effects MH - Male MH - Myocardium/*cytology MH - RNA, Messenger/biosynthesis/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Stimulation, Chemical MH - Transforming Growth Factor beta/*biosynthesis/genetics/metabolism EDAT- 1995/10/01 00:00 MHDA- 1995/10/01 00:01 CRDT- 1995/10/01 00:00 PHST- 1995/10/01 00:00 [pubmed] PHST- 1995/10/01 00:01 [medline] PHST- 1995/10/01 00:00 [entrez] AID - S0022-2828(95)91983-X [pii] AID - 10.1016/s0022-2828(95)91983-x [doi] PST - ppublish SO - J Mol Cell Cardiol. 1995 Oct;27(10):2347-57. doi: 10.1016/s0022-2828(95)91983-x.