Varga Zoltan V, Giricz Zoltan, Bencsik Peter, Madonna Rosalinda, Gyongyosi Mariann, Schulz Rainer, Mayr Manuel, Thum Thomas, Puskas Laszlo G, Ferdinandy Peter
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, Budapest, H-1089, Hungary.
Curr Drug Targets. 2015;16(8):904-11. doi: 10.2174/1389450116666150427154203.
Ischemic heart disease including myocardial infarction develops on the basis of several risk-factors and comorbidities such as obesity, diabetes, hypertension, and hypercholesterolemia. Ischemic heart disease is the leading cause of mortality worldwide, therefore, identification of novel drug targets for cardioprotection is of great importance. Ischemic preconditioning, postconditioning, and remote conditioning trigger endogenous cardioprotective mechanisms that render the heart more resistant to lethal ischemic-reperfusion injury. However, major cardiovascular co-morbidities such as hyperlipidemia, diabetes, and their co-medications interfere with these cardioprotective mechanisms thereby limiting the efficacy of cardioprotective ischemic conditioning maneuvers. Ischemia reperfusion injury and cardioprotection by conditioning have been shown to affect global myocardial gene expression profile at the transcript level. Further understanding and the comprehensive analysis of the cardioprotective gene expression fingerprint in normal, protected, and in comorbid conditions may lead to identification of novel molecular targets for cardioprotection.
包括心肌梗死在内的缺血性心脏病是在肥胖、糖尿病、高血压和高胆固醇血症等多种风险因素和合并症的基础上发展而来的。缺血性心脏病是全球范围内的主要死因，因此，识别新的心脏保护药物靶点具有重要意义。缺血预处理、后处理和远程预处理可触发内源性心脏保护机制，使心脏对致命的缺血再灌注损伤更具抵抗力。然而，高脂血症、糖尿病等主要心血管合并症及其联合用药会干扰这些心脏保护机制，从而限制了心脏保护缺血预处理措施的疗效。缺血再灌注损伤和预处理诱导的心脏保护已被证明在转录水平上会影响整体心肌基因表达谱。进一步了解并综合分析正常、受保护和合并症状态下的心脏保护基因表达指纹，可能会识别出新的心脏保护分子靶点。
