This study was designed to evaluate the relationships between platelet cytosolic Ca2+ concentration ([Ca2+]i) and plasma lipids in patients with primary hypercholesterolemia. In a double-blind, placebo-controlled trial, we determined platelet [Ca2+]i in the presence and virtual absence of extracellular Ca2+ and the effects of prolonged treatment with pravastatin, a selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Platelet [Ca2+]i and membrane micro- viscosity were determined in 22 normotensive hypercholesterolemic men. Platelet [Ca2+]i was observed to vary with in vivo plasma lipid characteristics: in untreated patients, [Ca2+]i determined at low extracellular Ca2+ concentration was significantly associated with plasma triacylglycerols (P=.008) and with the total cholesterol to HDL cholesterol ratio (P=.044). Triacylglycerol levels also correlated inversely with the external Ca2+-dependent [Ca2+]i rise. Pravastatin treatment reduced plasma total cholesterol (-20±3%), LDL cholesterol (-30±3%), triacylglycerols (-17±6%), and apoB levels (-25±4%) and simultaneously decreased platelet [Ca2+]i measured in a low-Ca2+ medium by 14±6% (P=.03). However, [Ca2+]i values remained positively correlated with the total cholesterol to HDL cholesterol ratio (P=.04). Pravastatin treatment did not induce marked changes in membrane microviscosity, although the changes in trimethylaminodiphenyl-hexatriene anisotropy were inversely correlated with those of HDL cholesterol. These results indicate that plasma lipids can modulate cytosolic Ca2+ in platelets by affecting Ca2+ transport pathways that are dependent and independent of Ca2+ influx.
CITATION STYLE
Le Quan Sang, K. H., Levenson, J., Megnien, J. L., Simon, A., & Devynck, M. A. (1995). Platelet Cytosolic Ca2+ and Membrane Dynamics in Patients with Primary Hypercholesterolemia: Effects of Pravastatin. Arteriosclerosis, Thrombosis, and Vascular Biology, 15(6), 759–764.
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