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.
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ABSTRACT: In recent years, platelet proteomics has been applied successfully to the study of cardiovascular diseases (CVDs). It is very well known that platelets play a pivotal role in the pathophysiological mechanisms underlying many CVDs, especially acute coronary syndromes (ACSs), since they are implied in thrombus formation after atheroma plaque rupture. This is the reason why molecules involved in platelet activation and aggregation are primary targets for treatment of ACSs. Many efforts are aimed at finding drugs that inhibit platelet activation; however it is difficult to separate the therapeutic benefits from harmful effects because pathological and physiological functions of platelets are due to the same mechanisms. Given that platelets lack a nucleus, proteomics is regarded as an ideal method to approach their biochemistry. Current platelet proteomic studies are focusing on the identification of platelet molecular and functional changes in normal and pathological states, enriching the comprehension of platelet biological function, and screening for new biomarkers and antiplatelet agents. In the present article, we introduce the reader to platelet biology and function, and revise recent advances in platelet proteomics applied to the study of CVDs, including a special emphasis on sample preparation requirements for proteome analysis of platelet clinical samples.10/2014; DOI:10.1016/j.trprot.2014.09.002