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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:759-764.)
© 1995 American Heart Association, Inc.

Articles

Platelet Cytosolic Ca²⁺ and Membrane Dynamics in Patients With Primary Hypercholesterolemia

Effects of Pravastatin

Kim-Hanh Le Quan Sang; Jaime Levenson; Jean-Louis Megnien; Alain Simon; Marie-Aude Devynck

From Pharmacologie, CNRS URA 1482, Faculté de Médecine Necker-Enfants Malades (K.-H.L.Q.S., M.-A.D.), and Centre de Médecine Préventive Cardiovasculaire, INSERM U28, Hôpital Broussais (J.L., J.-L.M., A.S.), Paris, France.

Abstract 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 microviscosity 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 trimethylaminodiphenylhexatriene 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.

Key Words: primary hypercholesterolemia • cytosolic Ca²⁺ concentration • membrane fluidity • platelets • pravastatin

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