The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

Abstract

Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.angiogenesis; arteriogenesis; redox-dependent signaling; mitochondria THIS ARTICLE is part of a collection on Mitochondria in Cardiovascular Physiology and Disease. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.

Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone

“…In isolated brain mitochondria, cultured neurons, astroglia and cerebral vascular endothelium, and intact cerebral vascular endothelium and VSM, the agent BMS-191095 causes mitochondrial depolarization without ROS production and promotes diverse cellular responses such as pre-/post-conditioning and VSM relaxation; thus, mitochondrial depolarization alone is sufficient to activate distinct cellular signaling pathways (12,15,64,86,88,89). Our findings with BMS-191095 are supported by results from other laboratories (126,143,144) and by other experimental approaches in our laboratory (41).…”

“…It also has been reported that a genetic deficiency of MnSOD in mice increases basal superoxide levels in cerebral arteries and aorta (10). Moreover, Pung et al have shown that chronic inhibition of Complex I by rotenone blocks ischemia induced collateral artery growth in the coronary circulation via activation of adenosine monophosphate-activated kinase and the subsequent inhibition of mechanistic target of rapamycin (mTOR) and p70 ribosomal S6 kinase (126). Higher levels of cellular ROS, such as occurs during injury and disease, can lead to cell death via both mitochondrial-and nonmitochondrial-mediated pathways, especially in metabolically compromised conditions (6,23,29,38,93,138).…”

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

“…It has been found that endothelial cell dysfunction affects the diffusion rate of oxygen across the arteriolar vessel wall [49,50]; however, these observations require further discussion. In endothelial cells, due in larger part to the unique nature of endothelium's limited metabolic demands, mtROS primarily play a prominent role as cell-signaling molecules [51,52]. Vascular endothelial cells overwhelmingly rely on glycolysis rather than the TCA cycle for cellular ATP needs [53,54].…”

Mitochondrial Mechanisms in Cerebral Vascular Control: Shared Signaling Pathways with Preconditioning

“…It also has been reported that a genetic deficiency of MnSOD in mice increases basal superoxide levels in cerebral arteries and aorta [10]. Additionally, Chilian et al have shown that chronic inhibition of Complex I by rotenone blocks ischemia induced collateral artery growth in the coronary circulation via activation of adenosine monophosphate activated kinase, and the subsequent inhibition of mTOR and p70 ribosomal S6 kinase [119]. Higher levels of cellular ROS, such as occurs during injury, can lead to cell death via both mitochondrial- and non-mitochondrial-pathways, especially in metabolically compromised conditions [57,89].…”