Mitochondria‐targeted antioxidant (MitoQ) ameliorates age‐related arterial endothelial dysfunction in mice

作者：Rachel A. Gioscia‐Ryan, Thomas J. LaRocca, Amy L. Sindler, Melanie C. Zigler, Michael P. Murphy, Douglas R. Seals · 发表于：The Journal of Physiology · 年份：2014 · DOI：10.1113/jphysiol.2013.268680 · 被引用次数：263 · 研究领域：Mitochondrial Function and Pathology、Nitric Oxide and Endothelin Effects、Redox biology and oxidative stress

Key points The development of age‐related arterial endothelial dysfunction, a key antecedent of increased cardiovascular disease (CVD) risk, is mediated largely by reduced nitric oxide bioavailability as a consequence of oxidative stress. Mitochondria are critical signalling organelles in the vasculature, which, when dysregulated, become a source of excessive reactive oxygen species; the role of mitochondria‐derived oxidative stress in age‐related vascular dysfunction is unknown. We show that a mitochondria‐targeted antioxidant, MitoQ, ameliorates vascular endothelial dysfunction in old mice and that these improvements are associated with the normalization of mitochondria‐derived oxidative stress and markers of arterial mitochondrial health. These results indicate that mitochondria‐derived oxidative stress is an important mechanism underlying the development of age‐related vascular endothelial dysfunction and therefore may be a promising therapeutic target. Mitochondria‐targeted antioxidants represent a novel strategy for preserving healthy vascular endothelial function in primary ageing and preventing age‐related CVD in humans. Abstract Age‐related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is...