The research project that is being proposed by Dr. Justice will increase our understanding of the mechanisms responsible for the modulation of nitric oxide synthase activity and nitric oxide production in response to hypoxemia. Ischemia and reperfusion, as a consequence of myocardial infarction, result in marked changes in the coronary microcirculation. Previous studies have shown that the endothelium of resistance arterioles is exposed for prolonged periods of time to low oxygen tension. It is the overall goal of this project to ascertain the effects of hypoxia on nitric oxide synthase and determine the mechanism responsible for increased nitric oxide production previously seen in response to hypoxia. The rationale for this research is firmly based upon extensive preliminary data, as well as previously published data demonstrating that the endothelium in the coronary microcirculation is importantly altered by low oxygen tension. This research will provide basic cellular and biochemical mechanisms underlying the functional responses we have previously observed in resistance arterioles. Utilizing tissue culture cells coupled with biochemical and molecular biology methods, the research will achieve three specific aims: 1) Determine if oxygen tension modulates nitric oxide production and eNOS protein levels in endothelial cells 2) Ascertain the mechanism(s) of NO and eNOS modulation in response to altered oxygen tension 3) Compare nitric oxide production, eNOS activity, and eNOS message in both resistance and conduit artery endothelium in response to hypoxia. The resources of the laboratory, current expertise, preliminary data, and experience of Dr. Justice strongly support the feasibility of this research.
| Drosatos-Tampakaki, Zoi; Drosatos, Konstantinos; Siegelin, Yasemin et al. (2014) Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis, while oleic acid-induced triglyceride formation prevents it. J Bone Miner Res 29:1183-95 |
| Justice, J M; Tanner, M A; Myers, P R (2000) Endothelial cell regulation of nitric oxide production during hypoxia in coronary microvessels and epicardial arteries. J Cell Physiol 182:359-65 |
