Department of Medicine, The Hatter Cardiovascular Institute, University College London Hospital, London WC1E 6HX, UK.
Cardiovasc Res. 2010 Oct 1;88(1):58-66. doi: 10.1093/cvr/cvq195. Epub 2010 Jun 16.
The endothelium is vital to the proper functioning in the heart, in particular due to its production of nitric oxide (NO) which regulates vascular tone. Damage to the endothelium contributes to the development of atherosclerosis, and hence to possible myocardial infarction and subsequent heart failure. Like most cells, endothelial cells contain mitochondria, despite their having relatively little dependence on oxidative phosphorylation for ATP production. However, endothelial mitochondria are centrally involved in maintaining the fine regulatory balance between mitochondrial calcium concentration, reactive oxygen species (ROS) production, and NO. This raises the question of whether damage to endothelial mitochondria would have repercussions in terms of the development of heart disease. In fact, increasingly nuanced techniques enabling restricted transgenic expression of antioxidant proteins in mice has demonstrated that mitochondrial ROS do contribute to endothelial damage. New pharmaceutical approaches designed to target protective molecules such as ROS scavengers to the mitochondria promise to be effective in preventing heart disease. As well as protecting cardiomyocytes, these drugs may have the added benefit of preventing damage to the endothelial mitochondria. However, much remains to be done in understanding the contribution that mitochondria make to endothelial function.
内皮细胞对于心脏的正常功能至关重要，特别是因为它能产生一氧化氮（NO），从而调节血管张力。内皮细胞的损伤会导致动脉粥样硬化的发展，从而可能导致心肌梗死和随后的心力衰竭。与大多数细胞一样，内皮细胞含有线粒体，尽管它们对氧化磷酸化产生 ATP 的依赖相对较小。然而，内皮细胞线粒体在维持线粒体钙浓度、活性氧（ROS）产生和 NO 之间的精细调节平衡方面起着核心作用。这就提出了一个问题，即内皮细胞线粒体的损伤是否会对心脏病的发展产生影响。事实上，越来越多的技术能够使抗氧化蛋白在小鼠中进行受限的转基因表达，这表明线粒体 ROS 确实会导致内皮细胞损伤。旨在将 ROS 清除剂等保护分子靶向线粒体的新药物治疗方法有望在预防心脏病方面取得疗效。这些药物不仅可以保护心肌细胞，还有助于防止内皮细胞线粒体损伤。然而，在了解线粒体对内皮功能的贡献方面，还有很多工作要做。
