Angiotensin II induction of smooth muscle extracellular matrix synthesis in culture

Abstract

Treatment of cultured rat smooth muscle cells with angiotensin II stimulated the synthesis of extracellular matrix macromolecules. Previous studies have demonstrated the rapid induction of thrombospondin expression by cultured smooth muscle cells treated with the vasoconstrictor peptide, and this study demonstrates that tenascin production is induced in a similar manner. Angiotensin II stimulates the production of a number of growth factors by cultured smooth muscle cells, and this may be the mechanism of induction of the extracellular matrix glycopeptides thrombospondin and tenascin. Deposition of immunoreactive thrombospondin into extracellular matrix material elaborated by cultured cells was more rapid in response to platelet-derived growth factor A-chain homodimer than in response to angiotensin II or transforming growth factor-β1. Transforming growth factor-β1 inhibited the proliferation of cultured smooth muscle cells prior to their onset of matrix elaboration in culture; however, once this had commenced, growth factor treatment resulted in the stimulation of proliferation. Angiotensin-induced endothelin production by cultured smooth muscle cells did not contribute to the stimulated synthesis of extracellular matrix glycoconjugates elicited by angiotensin II, since the composition of matrix material elaborated by cells exposed to endothelin directly was the same as controls.