Ravassa Susana, Zudaire Amaia, Díez Javier
Área de Ciencias Cardiovasculares, Centro para la Investigación Médica Aplicada, Universidad de Navarra, Pamplona, España.
Endocrinol Nutr. 2012 Nov;59(9):561-9. doi: 10.1016/j.endonu.2012.07.007. Epub 2012 Sep 30.
During myocardial infarction (MI), a variety of mechanisms contribute to activation of cell death processes in cardiomyocytes, which determines the final MI size, subsequent mortality, and post-MI remodeling. The deleterious mechanisms activated during the ischemia and reperfusion phases in MI include oxygen deprival, decreased availability of nutrients and survival factors, accumulation of waste products, generation of oxygen free radicals, calcium overload, neutrophil infiltration in the ischemic area, depletion of energy stores, and opening of the mitochondrial permeability transition pore, all of them contributing to activation of apoptosis and necrosis in cardiomyocytes. Glucagon-like peptide-1 [GLP-1 (7-36) amide] has gained relevance in recent years for metabolic treatment of patients with type 2 diabetes mellitus. Cytoprotection of different cell types, including cardiomyocytes, is among the pleiotropic actions reported for GLP-1. This paper reviews the most relevant experimental studies that have contributed to a better understanding of the molecular mechanisms and intracellular pathways involved in cardioprotection induced by GLP-1 and analyzes in depth its potential role as a therapeutic target both in the ischemic and reperfused myocardium and in other conditions that are associated with myocardial remodeling and heart failure.
在心肌梗死（MI）期间，多种机制促使心肌细胞发生细胞死亡过程，这决定了最终的心肌梗死面积、后续死亡率以及心肌梗死后的重塑。心肌梗死缺血和再灌注阶段激活的有害机制包括缺氧、营养物质和存活因子供应减少、废物积累、氧自由基生成、钙超载、缺血区域中性粒细胞浸润、能量储备耗竭以及线粒体通透性转换孔开放，所有这些都促使心肌细胞发生凋亡和坏死。近年来，胰高血糖素样肽-1[GLP-1（7-36）酰胺]在2型糖尿病患者的代谢治疗中具有重要意义。包括心肌细胞在内的不同细胞类型的细胞保护作用是GLP-1所报道的多效性作用之一。本文综述了最相关的实验研究，这些研究有助于更好地理解GLP-1诱导心脏保护所涉及的分子机制和细胞内途径，并深入分析其在缺血和再灌注心肌以及与心肌重塑和心力衰竭相关的其他情况下作为治疗靶点的潜在作用。
