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急性冠脉综合征中与“困惑”循环血小板相关的蛋白质组学变化。

Proteomic changes related to "bewildered" circulating platelets in the acute coronary syndrome.

机构信息

Cardiovascular Research Unit, Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain.

出版信息

Proteomics. 2011 Aug;11(16):3335-48. doi: 10.1002/pmic.201000708. Epub 2011 Jul 14.

Abstract

Acute coronary syndromes (ACS) are associated with platelet activation. The aim of the present study was to study the protein expression level associated with glycolysis, oxidative stress, cytoskeleton and cell survival in platelets obtained during an ACS. Platelets from 42 coronary ischemic patients, divided into patients admitted within 24 h after the onset of chest pain (ACS group; n=16) and patients with stable coronary ischemic disease (CAD, n=26), were analyzed using proteomics. The expression levels of proteins involved in cellular cytoskeleton (F-actin capping, β-tubulin, α-tubulin isotypes 1 and 2, vinculin, vimentin and two Ras-related protein Rab-7b isotypes), glycolysis pathway (glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase and two pyruvate kinase isotypes) and cellular-related antioxidant system (manganese superoxide dismutase) and even the expression and activity of glutathione-S-transferase were significantly reduced in platelets from ACS patients compared to CAD patients. Moreover, reduction in the expression of proteins associated with cell survival such as proteasome subunit β type 1 was also observed in ACS platelets compared with CAD platelets. Principal component and logistic regression analysis suggested the existence of factors (proteins) expressed in the platelets inversely associated with acute coronary ischemia. In summary, these results suggest the existence of circulating antioxidant, cytoskeleton and glycolytic-"bewildered" platelets during the acute phase of a coronary event.

摘要

急性冠状动脉综合征(ACS)与血小板激活有关。本研究旨在研究 ACS 期间获得的血小板中与糖酵解、氧化应激、细胞骨架和细胞存活相关的蛋白质表达水平。使用蛋白质组学分析了 42 名冠状动脉缺血患者的血小板,这些患者分为胸痛发作后 24 小时内入院的患者(ACS 组,n=16)和稳定型冠状动脉缺血性疾病(CAD,n=26)患者。与 CAD 患者相比,ACS 患者的血小板中涉及细胞骨架的蛋白质(F-肌动蛋白盖帽、β-微管蛋白、α-微管蛋白同工型 1 和 2、踝蛋白、波形蛋白和两种 Ras 相关蛋白 Rab-7b 同工型)、糖酵解途径(甘油醛-3-磷酸脱氢酶、乳酸脱氢酶和两种丙酮酸激酶同工型)和细胞相关抗氧化系统(锰超氧化物歧化酶)的表达水平甚至谷胱甘肽-S-转移酶的表达和活性均显著降低。此外,与 CAD 血小板相比,ACS 血小板中与细胞存活相关的蛋白质(如蛋白酶体亚基β 型 1)的表达减少。主成分和逻辑回归分析表明,血小板中存在与急性冠状动脉缺血呈负相关的表达因子(蛋白质)。总之,这些结果表明,在冠状动脉事件的急性期存在循环抗氧化剂、细胞骨架和糖酵解“困惑”的血小板。

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