The role of nitrite in cutaneous wound healing: This project focuses on the potential role of an alternative NO pathway in normal wound healing. NO has been show to be essential in wound healing and the expression of eNOS and iNOS have been shown to be reduced in diabetics who suffer from impaired wound healing. There is also an upregulation of arginase I expression in diabetics and may further deplete NO by competing for arginine, the substrate for NO production. Nitrite can be converted to NO through enzymatic and nonenzymatic pathways and may provide a source of NO in wound healing. Studies are currently underway in normal and diabetic mice.
The role of inhaled carbon monoxide in the prevention of intimal hyperplasia. We have previously demonstrated that inhaled CO can significantly reduce intimal hyperplasia. It appears to be alter the behavior of macrophages to support an anti-inflammatory and antiproliferative phenotype. Studies are ongoing to understand the mechanisms by which inhaled CO mediates these changes. This comes from the finding that direct actions of CO on macrophages cannot reproduce the effects achieved by inhaled CO.
The role of purinergic signaling in the process of angiogenesis and collaterogenesis. Purines are released by tissues during stress and can play important roles in signaling. We have identified that the inhibition of the purinergic receptor P2Y2 can impair endothelial tube formation and the absence of this receptor leads to profound ischemic changes in a hindlimb ischemia model in mice. Studies are underway to evaluate the role of this receptor in angiogenesis versus collateral formation.
The role of CO in abdominal aortic aneurysm formation. Because our other studies have shown that CO is strongly anti-inflammatory, we are investigating its role in the development of AAAs which is characterized by inflammation and tissue degeneration. We have early studies that show inhaled CO can reduce the growth of aortic dilation in a calcium phosphate model of AAA. Further studies are directed at the effects of CO on complement and matrix degradation in aneurysm disease.