Mildly oxidised low density lipoprotein induces platelet shape change via Rho-kinase-dependent phosphorylation of myosin light chain and moesin

Oxidised low density lipoprotein (LDL) plays an important role in the patho genesis of atherosclerosis, Here me demonstrate that mildly oxidised (mox) LDL engages the GTPase Rho and its effector molecule p160 Rho-kinase to ind uce phosphorylation of myosin light chain and of moesin leading to platelet shape change, Pretreatment of platelets with the selective Rho inhibitor C 3-transferase from Clostridium botulinum or with the Rho-kinase inhibitor Y -27632 blocked mox-LDL-induced myosin light chain phosphorylation, moesin p hosphorylation and shape change. Mos-LDL did not induce an increase in cyto solic Ca2+ during shape change. We propose that Rho/Rho-kinase inhibition c ould be a strategy for prevention of the pathologic platelet activation dur ing atherogenesis. (C) 2000 Federation of European Biochemical Societies.