Elevated cholesterol reduces acetylsalicylic acid-mediated platelet acetylation.
We describe the role of plasma and platelet cholesterol content in the ability of acetylsalicylic acid (ASA) to acetylate platelet proteins and inhibit platelet function. Platelet susceptibility to ASA was monitored in subjects differing in plasma total cholesterol and in suspensions of cholesterol-enriched or cholesterol-depleted platelets. Platelets from subjects with higher plasma cholesterol (>6 mmol/l) showed reduced platelet sensitivity to ASA (inhibition of platelet aggregation and thromboxane generation by 60% and 68% in 'lower-' vs. 32% and 56% in 'higher-cholesterol' donors; n=13 in each group; p=0.056 and p<0.04, respectively). [Acetyl-1-(14)C] incorporation to platelet proteins in subjects with higher plasma cholesterol was significantly reduced (11.0 vs. 14.6 nmol/g protein, p<0.0001) and correlated significantly with blood total cholesterolemia (R(K)=-0.430, p<0.003) and LDL-cholesterol (R(K)=-0.349, p<0.012), but not with platelet cholesterol content. In conclusion, elevated plasma cholesterol is an important determinant of ASA-induced acetylation of platelets and platelet diminished sensitivity to ASA. The molecular basis of such an association remains obscure, notwithstanding it may constitute a link between sub-optimal platelet response to aspirin and lipid metabolic disorders.
Boncler
Magdalena
M
Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Medical University Hospital No. 2, 113 Zeromskiego Street, 90-549 Lodz, Poland.
Gresner
Peter
P
Nocun
Marek
M
Rywaniak
Joanna
J
Dolnik
Martin
M
Rysz
Jacek
J
Wilk
Radoslaw
R
Czyz
Malgorzata
M
Markuszewski
Leszek
L
Banach
Maciej
M
Watala
Cezary
C
D000107:Acetylation; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D006801:Humans; D008051:Lipid Bilayers; D010974:Platelet Aggregation / Q000187:drug effects; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D008051:Lipid Bilayers; D013931:Thromboxanes; D002784:Cholesterol; D001241:Aspirin