title: Elevated cholesterol reduces acetylsalicylic acid-mediated platelet acetylation.
abstract: 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.
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Medical University Hospital No. 2, 113 Zeromskiego Street, 90-549 Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Boncler
authors.forename: Peter
authors.initials: P
authors.lastname: Gresner
authors.forename: Marek
authors.initials: M
authors.lastname: Nocun
authors.forename: Joanna
authors.initials: J
authors.lastname: Rywaniak
authors.forename: Martin
authors.initials: M
authors.lastname: Dolnik
authors.forename: Jacek
authors.initials: J
authors.lastname: Rysz
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Wilk
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Czyz
authors.forename: Leszek
authors.initials: L
authors.lastname: Markuszewski
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
authors.forename: Cezary
authors.initials: C
authors.lastname: Watala
mesh_terms: 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
chemical_list: D008051:Lipid Bilayers; D013931:Thromboxanes; D002784:Cholesterol; D001241:Aspirin