Energy dependent reversal of endothelial dysfunction in wound healing

 描述(由申请人提供)： 内皮细胞衬里产生一氧化氮(NO)等维持血管内稳态的关键物质。影响心脏(冠状动脉疾病)和骨骼肌(外周动脉疾病)的心血管疾病可归因于内皮细胞的病理性转变，从血管活性、抗血栓和再生的NO产生细胞转变为血管扩张受损、血栓形成增加和细胞修复能力丧失的细胞，因为NO的产生受到抑制。心血管危险因素，如年龄、高血压、高脂血症、创伤后应激障碍和吸烟，诱导炎症信号，刺激这种病理变化。内皮功能障碍的一个表现是糖尿病和外周动脉疾病患者的慢性溃疡创面。我们国家的退伍军人患慢性溃疡的风险很高，因为他们拥有许多这些心脏风险因素。退伍军人管理职业发展奖(CDA-2)的前提是光能产生一种新的方法来增加被内皮功能障碍清除的NO，未来可能会导致有针对性地促进伤口愈合的新型血管疗法的发展。这些研究旨在验证光能释放NO的假设。 缺血组织。这种替代的NO来源有可能改善NO产生减弱的区域的内皮功能，从而改善血管的反应性和伤口愈合。我们的假设将通过靶向一组已知的产生和结合NO的蛋白质并测量其在能量暴露前后的产生来检验。我们还将测量在生理条件和炎症应激下，能量对刺激血管扩张和伤口愈合的影响。从这项研究中获得的信息将扩大我们对细胞中重要的无存储存在的地方的理解，以及能量如何刺激这些存储以改善炎症性疾病中内皮细胞的动态平衡。

 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.