Energy dependent reversal of endothelial dysfunction in wound healing

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 DESCRIPTION (provided by applicant): The endothelial lining produces key substances such as nitric oxide (NO) for the maintenance of vascular homeostasis. Cardiovascular diseases affecting the heart (coronary artery disease) and skeletal muscle (peripheral artery disease) can be attributed to a pathological transformation of the endothelium from a NO producing cell which is vasoactive, antithrombotic, and regenerative; to a cell which exhibits impaired vasodilation, increased thrombus formation, and a lost capacity for cellular repair because NO production is inhibited. Cardiovascular risk factors such as age, hypertension, hyperlipidemia, PTSD and tobacco use induce inflammatory signals which stimulate this pathological transformation. One manifestation of endothelial dysfunction is the chronic ulcerative wounds seen in patients with diabetes and peripheral artery disease. Our nation's veterans are at high risk for chronic ulcerated wounds because they possess many of these cardiac risk factors. This Veterans Administration Career Development Award (CDA-2) is conceived on the premise that light energy produces a novel means for increasing NO which is scavenged by endothelial dysfunction, and in the future may lead to the development of novel vascular therapies targeted to improve wound healing. These investigations are directed to test the hypothesis that light energy can release NO specifically to ischemic tissues. This alternative source of NO has the potential to improve endothelial function in regions where NO production is attenuated, thereby improving vessel reactivity and wound healing. Our hypothesis will be tested by targeting a defined set of proteins known to produce and bind NO and measure its production before and after energy exposure. We will also measure the impact of energy to stimulate vasodilation and wound healing under physiological conditions and inflammatory stress. The information gained from this investigation will expand our understanding of where important NO stores in the cell exist, and how energy can stimulate these stores to improve endothelial cell homeostasis in inflammatory disease.