Oxygen Species in Coronary Collateral Growth

38 Coronary collateral growth is a process involving coordination between growth factors 39 expressed in response to ischemia and mechanical forces. Underlying this response is 40 proliferation of vascular smooth muscle and endothelial cells, resulting in an 41 enlargement in the caliber of arterial-arterial anastomoses, i.e. a collateral vessel, 42 sometimes as much as an order of magnitude. An integral element of this cell 43 proliferation is the process known as phenotypic switching in which cells of a particular 44 phenotype, e.g., contractile vascular smooth muscle, must change their phenotype in 45 order to proliferate. Phenotypic switching requires that protein synthesis occurs and 46 different kinase signaling pathways become activated, necessitating energy to make the 47 switch. Moreover, kinases, utilizing ATP to phosphorylate their targets, have an energy 48 requirement themselves. Mitochondria play a key role in the energy production that 49 enables phenotypic switching, but under conditions where mitochondrial energy 50 production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In 51 addition, we discuss the potential importance of uncoupling proteins as modulators of 52 mitochondrial ROS production and bioenergetics, as well as the role of AMP kinase as 53 an energy sensor upstream of mTOR, the master regulator of protein synthesis. 54 55 56 57