School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA.
Circ Res. 2012 Oct 12;111(9):1222-36. doi: 10.1161/CIRCRESAHA.112.265660.
Ischemic heart disease is a significant cause of morbidity and mortality in Western society. Although interventions, such as thrombolysis and percutaneous coronary intervention, have proven efficacious in ischemia and reperfusion injury, the underlying pathological process of ischemic heart disease, laboratory studies suggest further protection is possible, and an expansive research effort is aimed at bringing new therapeutic options to the clinic. Mitochondrial dysfunction plays a key role in the pathogenesis of ischemia and reperfusion injury and cardiomyopathy. However, despite promising mitochondria-targeted drugs emerging from the laboratory, very few have successfully completed clinical trials. As such, the mitochondrion is a potential untapped target for new ischemic heart disease and cardiomyopathy therapies. Notably, there are a number of overlapping therapies for both these diseases, and as such novel therapeutic options for one condition may find use in the other. This review summarizes efforts to date in targeting mitochondria for ischemic heart disease and cardiomyopathy therapy and outlines emerging drug targets in this field.
缺血性心脏病是西方社会发病率和死亡率的重要原因。尽管溶栓和经皮冠状动脉介入等干预措施已被证明对缺血再灌注损伤有效,但实验室研究表明,缺血性心脏病的潜在病理过程还可以进一步得到保护,大量的研究工作旨在将新的治疗选择推向临床。线粒体功能障碍在缺血再灌注损伤和心肌病的发病机制中起关键作用。然而,尽管有一些有前景的靶向线粒体的药物从实验室中出现,但很少有药物成功完成临床试验。因此,线粒体是缺血性心脏病和心肌病新疗法的潜在未开发靶点。值得注意的是,这两种疾病有许多重叠的治疗方法,因此一种疾病的新治疗选择可能会在另一种疾病中得到应用。这篇综述总结了目前针对缺血性心脏病和心肌病治疗靶向线粒体的努力,并概述了该领域新兴的药物靶点。