Endothelial mitochondria and heart disease.
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.
Davidson
Sean Michael
SM
Department of Medicine, The Hatter Cardiovascular Institute, University College London Hospital, London WC1E 6HX, UK. s.davidson@ucl.ac.uk
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002118:Calcium