Platelet cytosolic Ca2+ and membrane dynamics in patients with primary hypercholesterolemia. Effects of pravastatin.
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 Ca(2+)-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). Prvastatin 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.
Le Quan Sang
K H
KH
CNRS URA 1482, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Levenson
J
J
Megnien
J L
JL
Simon
A
A
Devynck
M A
MA
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure*; D002118:Calcium / Q000097:blood*; D002462:Cell Membrane / Q000502:physiology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003600:Cytosol / Q000378:metabolism*; D004311:Double-Blind Method; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008560:Membrane Fluidity; D008875:Middle Aged; D010919:Placebos; D017035:Pravastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014783:Viscosity
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D014280:Triglycerides; D017035:Pravastatin; D002118:Calcium