Article: PDF OnlyScott-Burden Timothy; Resink, Therese J.; Hahn, Alfred W. A.; Bühler, Fritz R.Journal of Cardiovascular Pharmacology: 1990 - p S17-S20 Free Abstract Summary Vascular smooth muscle cells (VSMCs), unlike cardiac or skeletal myocytes, are capable of undergoing reversible phenotypic modulation from “contractile” to “proliferative/synthetic” cells in vivo. We have investigated the ability of angiotensin II (Ang II) to influence this process via modulation of extracellular matrix synthesis. Ang II induced a rapid (within 2 h), dose (10−6-10−9M)-dependent stimulation (14-fold) of thrombospondin (TSP) gene expression in rat VSMCs in the absence of additional factors. This was followed by an enhanced platelet-derived growth factor (PDGF) A chain and transforming growth factor-β (TGFβ) gene expression. These effects of Ang II could be negated by the simultaneous addition of saralasin (IC50 ∼ 10−9M for Ang II at 10−7M) to cells. Transcription levels for TSP were further enhanced (to 28 × control values) by 6 h, at which time the synthesis of PDGF A chain mRNA was maximal. Although exposure of cells to TSP (5 × 10−8M) stimulated signal transduction pathways, it did not enhance levels of either PDGFA or TGFβ transcripts. The glycoconjugate content of extracellular matrices elaborated by cells chronically exposed to Ang II was elevated compared to control cultures and there was a small increase in cell number. Copyright © 1990 Wolters Kluwer Health, Inc. All rights reserved.