title: A novel insight into the mechanism of pulmonary hypertension involving caveolin-1 deficiency and endothelial nitric oxide synthase activation.
abstract: Severe pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary vascular resistance and vascular remodeling leading to right heart failure and early death. Our recent studies with the use of the novel mouse model with genetic deletions of caveolin-1 (Cav1) and endothelial nitric oxide synthase (eNOS) (NOS3) have demonstrated that persistent eNOS activation in Cav1(-/-) lungs results in tyrosine nitration of protein kinase G (PKG) and impairment of its activity, which thereby induces PH. The finding of eNOS activation and PKG nitration concomitant with Cav1 deficiency was recapitulated in lungs from patients with idiopathic pulmonary arterial hypertension. These data suggest targeting PKG nitration has potential value for the treatment of PH. Here, we will review the current knowledge about Cav1-regulated eNOS activity and its fundamental role in the pathogenesis of PH.
authors.affiliation: Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA. yyzhao@uic.edu <yyzhao@uic.edu>
authors.forename: You-Yang
authors.initials: YY
authors.lastname: Zhao
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000172:deficiency* / Q000235:genetics; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D014443:Tyrosine; D052250:Nitric Oxide Synthase Type III; D017869:Cyclic GMP-Dependent Protein Kinases
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