Platelet-vessel wall interactions, focal adhesions, and the mechanism of action of endothelial factors.

Abstract

Endothelial cells produce a variety of vasoactive substances including prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF/NO) which are potent inhibitors of platelet adhesion/aggregation and vascular smooth muscle cell contraction/proliferation. PGI2 and EDRF elevate cAMP or cGMP, respectively, in vascular cells and other targets. The intracellular effects of cAMP and cGMP in vascular smooth muscle cells and platelets are primarily mediated by the family of cAMP- and cGMP-dependent protein kinases and their substrates. Important effector systems include enzymes, channels and regulatory proteins responsible for the regulation of intracellular Ca++. Other evidence suggests that VASP, a focal adhesion protein phosphorylated in platelets and smooth muscle cells in response to PGI2 and EDRF, is important for the regulation of integrins and cell-matrix interactions.