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 pathogenesis of atherosclerosis. Here we demonstrate that mildly oxidised (mox) LDL engages the GTPase Rho and its effector molecule p160 Rho-kinase to induce phosphorylation of myosin light chain and of moesin leading to platelet shape change. Pretreatment of platelets with the selective Rho inhibitor C3-transferase from Clostridium botulinum or with the Rho-kinase inhibitor Y-27632 blocked mox-LDL-induced myosin light chain phosphorylation, moesin phosphorylation and shape change. Mox-LDL did not induce an increase in cytosolic Ca(2+) during shape change. We propose that Rho/Rho-kinase inhibition could be a strategy for prevention of the pathologic platelet activation during atherogenesis.
Retzer
M
M
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Pettenkoferstr. 9, 80336, Munich, Germany.
Siess
W
W
Essler
M
M
D000577:Amides / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008840:Microfilament Proteins; D018994:Myosin Light Chains; D011725:Pyridines; C099252:oxidized low density lipoprotein; C108830:Y 27632; C071058:moesin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; D002118:Calcium