Elevated cholesterol reduces acetylsalicylic acid-mediated platelet acetylation

被引:25
作者
Boncler, Magdalena
Gresner, Peter
Nocun, Marek
Rywaniak, Joanna
Dolnik, Martin
Rysz, Jacek
Wilk, Radoslaw
Czyz, Malgorzata
Markuszewski, Leszek
Banach, Maciej
Watala, Cezary
机构
[1] Med Univ Lodz, Med Univ Hosp, Dept Haemostasis & Haemostat Disorder, PL-90549 Lodz, Poland
[2] Med Univ Lodz, Med Univ Hosp, Dept Family Med 2, PL-90549 Lodz, Poland
[3] Nofer Inst Occupant Med, Dept Immunotoxicol, Lodz, Poland
[4] Comenius Univ, Dept Nucl Phys & Biophys, Div Biomed Phys, Bratislava 81806, Slovakia
[5] Med Univ Lodz, Dept Biol Mol Canc, Lodz, Poland
[6] Med Univ Lodz, Med Univ Hosp, Dept Invasive Cardiol Cardiodiabetol & Cardiac Re, PL-90549 Lodz, Poland
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2007年 / 1770卷 / 12期
关键词
acetylsalicylic acid; aspirin resistance; cholesterol; platelet aggregation; platelet protein acetylation;
D O I
10.1016/j.bbagen.2007.09.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-l-C-14] 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 kappa=-0.430, p<0.003) and LDL-cholesterol (R kappa=-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. (C) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:1651 / 1659
页数:9
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