Superoxide and Vascular Function in Heart Failure

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DESCRIPTION (provided by applicant): Heart failure (HF) is an enormously important clinical problem. Impairment of endothelial function is associated with HF, and may contribute to the progression of HF by increasing ventricular afterload. As oxidative stress is a important determinant of endothelial function, these studies aim to: 1) determine the role of extracellular superoxide dismutase (ecSOD), an important antioxidant, in protection of endothelial function in HF, and 2) determine the role of the intracellular copper-zinc SOD (CuZnSOD) in the protection of endothelial function in HF. For Aim 1, aortic rings from mice deficient in ecSOD will be studied ex vivo to determine the contribution of endogenous ecSOD to preservation of endothelial function in HF. Mice overexpressing human ecSOD will also be studied ex vivo to determine if increases in ecSOD can protect endothelial function in HF. In Aim 2, aortic rings from mice deficient in CuZnSOD, as well as rings from transgenic mice overexpressing CuZnSOD will be studied ex vivo to determine the role of intracellular superoxide scavenging in HF. Collectively, these studies will lend important insights into the role of oxidative stress and vascular function in HF.