title: Impact of clopidogrel and aspirin treatment on the expression of proteins in platelets from type-2 diabetic patients with stable coronary ischemia.
abstract: The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone.
authors.affiliation: Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid 28040, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Azcona
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: López Farré
authors.forename: Petra
authors.initials: P
authors.lastname: Jiménez Mateos-Cáceres
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura
authors.forename: Pablo
authors.initials: P
authors.lastname: Rodríguez
authors.forename: Javier
authors.initials: J
authors.lastname: Modrego
authors.forename: José J
authors.initials: JJ
authors.lastname: Zamorano-León
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D003327:Coronary Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010978:Platelet Factor 4 / Q000097:blood; D020543:Proteome / Q000032:analysis / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D003598:Cytoskeletal Proteins; D010975:Platelet Aggregation Inhibitors; D020543:Proteome; D010978:Platelet Factor 4; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin