RESUMO
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.
Assuntos
Aspirina/uso terapêutico , Doença das Coronárias/complicações , Diabetes Mellitus Tipo 2/complicações , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Proteoma/genética , Ticlopidina/análogos & derivados , Idoso , Sequência de Aminoácidos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Clopidogrel , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Proteínas do Citoesqueleto/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Quimioterapia Combinada , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Fator Plaquetário 4/sangue , Proteoma/análise , Ticlopidina/uso terapêuticoRESUMO
La disfunción endotelial es una patología que antecede a las patologías de origen vascular. La disfunción endotelial se ha definido como una reducción en la respuesta vasodilatadora dependiente del endotelio y del sistema del oxido nítrico (NO). Los mecanismos causantes de la disfunción endotelial no están totalmente definidos y en este artículo se hace una revisión de las más estudiadas. En este sentido, es conocido que cuando existe disfunción endotelial se favorece la activación de las plaquetas facilitándose la formación de trombos. Pero también las plaquetas podrían participar directamente en la génesis y progresión de la disfunción endotelial
Endothelial dysfunction is a pathology that appears early before any morphological vascular alteration could be detected. Endothelial dysfunction has been defined as a reduction in the endothelium and nitric oxide (NO)- dependente vasorelaxation response. The mechanisms involved in the genesis and development of endothelial dysfunction have not defined at all. In the present work, we have reviewer same of the main studied mechanisms associated with endothelial dysfunction. In this regard, it is well known that the existence of endothelial dysfunction provoked the activation of platelets although less is known if platelets by themselves could be also involved in the genesis and progression of endothelial dysfunction
Assuntos
Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Humanos , Endotélio/anormalidades , Endotélio/patologia , Inflamação/complicações , Inflamação/diagnóstico , Plaquetas , Arginina/antagonistas & inibidores , Moduladores da Angiogênese/uso terapêutico , Endotélio Vascular/patologia , Agregação Plaquetária , Agregação Plaquetária/fisiologiaRESUMO
AIM: To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed. METHODS: ET-1 (0.013 microg/min) was infused to male guinea-pigs for 45 min in the presence and absence of tirofiban, a nonpeptidic blocker of the glycoprotein IIb/IIIa receptor (GPIIb/IIIa). Tissue factor and COX-2 expression were determined by Western blot. RESULTS: No changes in mean arterial pressure and heart rate were detected. ET-1-infused guinea-pigs showed a marked increase in the number of platelets expressing activated GPIIb/IIIa receptors (0.8+/-0.03% vs. 6.5+/-0.2%; P<0.05). Tirofiban (10 microg/Kg bw/min) blunted ex vivo platelet aggregation in response to ADP, although only partially reduced COX-2 and tissue factor expression in both the myocardium and leukocytes of ET-1-infused guinea-pigs. The myocardium of platelet-depleted guinea-pigs also showed a reduced COX-2 expression after ET-1 infusion (57+/-3% reduction; P<0.05). In vitro studies demonstrated that platelets (10(7) and 10(9) platelets/well) enhanced ET-1 (10(-7) mol/l)-induced COX-2 expression in heart slices. CONCLUSION: ET-1 stimulated in vivo the expression of the pro-inflammatory proteins COX-2 and tissue factor in the myocardium and in leukocytes by a mechanism GPIIb/IIIa platelet receptors.
