Pulmonary arterial hypertension (PAH) is generally defined as a sustained elevation of pulmonary arterial pressure without left ventricular failure. Nitric Oxide (NO) is an endogenously produced, locally acting gas that exerts multiple actions that help to maintain lung vascular function, while development of PAH is associated with reduced lung vascular NO bioavailability. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is the critical enzyme for the degradation of endogenous NO synthase inhibitor ADMA to enhance NO production. Adenosine monophosphate-activated protein kinase (AMPK) is an enzyme that also exerts multiple actions to regulating cardiovascular function partially though modulating NO production. This dissertation tries to identify the effects of DDAH1 and AMPKα2 on hypoxia-induced pulmonary arterial hypertension and the underlying molecular mechanisms. The findings from these studies provide new insight into the molecular mechanism of the development of PAH and right heart hypertrophy/failure. The dissertation has been divided into 2 chapters. The first chapter is determining effect of DDAH1 gene deletion on hypoxia+SU5416-induced pulmonary arterial hypertension and the second chapter is determining effect of AMPKα2 gene deletion on hypoxia+SU5416-induced pulmonary arterial hypertension.
University of Minnesota Ph.D. dissertation. June 2015. Major: Kinesiology. Advisor: Arthur Leon. 1 computer file (PDF); vii, 147 pages.
Effects Of Dimethylarginine Dimethylaminohydrolase 1 And Adenosine Monophosphate-Activated Protein Kinase Alpha 2 Gene Deletion On Pulmonary Hypertension In Mice.
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