THE RENIN-ANGIOTENSIN SYSTEM AND EXTRACELLULAR-MATRIX

A hallmark of vascular disease is the inappropriate proliferative and synthetic behaviour of vascular smooth muscle cells. This phenotypical ly immature behaviour arises as a consequence of the myocytes undergoi ng phenotypic conversion and/or clonal proliferation of a ''fetal'' ty pe of smooth muscle cell preexisting in the vessel wall. De-differenti ation and initiation of proliferation is not only induced by endotheli al desquamation and acute exposure of smooth muscle cells to platelet- derived mitogens, but also occurs in the uninjured blood vessel. There fore normal components of the blood vessel are implicit in the patholo gical process. These include vasoconstrictor peptides, growth factor p eptides and extracellular matrix molecules. In vitro and in vivo exper imentation has indicated that while some of these compounds individual ly are only mild stimulators of smooth muscle proliferative metabolism , they may act synergistically to induce robust responses. Here we dis cuss the effects of the vasoconstrictor peptide angiotensin II, which can be locally generated within the vessel wall itself, on the express ion of extracellular matrix molecules in vitro and in vivo. We focus o n the angiotensin II-modulated expression of extracellular matrix glyc oproteins, e.g. thrombospondin, tenascin, fibronectin and laminin.