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Property "Has-20abstract" (as page type) with input value "Remodeling-20of-20the-20distal-20pulmonary-20artery-20wall-20is-20a-20characteristic-20feature-20of-20pulmonary-20hypertension-20(PH).-20In-20hypoxic-20pulmonary-20hypertension,-20the-20most-20substantial-20pathologic-20changes-20occur-20in-20the-20adventitia.-20Here,-20there-20is-20marked-20fibroblast-20proliferation-20and-20profound-20macrophage-20accumulation.-20These-20fibroblasts-20(PH-2DFibs)-20maintain-20a-20hyperproliferative,-20apoptotic-20resistant-20and-20pro-2Dinflammatory-20phenotype-20in-20-27-27ex-20vivo-27-27-20culture.-20Considering-20that-20a-20similar-20phenotype-20is-20observed-20in-20cancer-20cells,-20where-20it-20has-20been-20associated-20at-20least-20in-20part-20with-20specific-20alterations-20in-20mitochondrial-20metabolism,-20we-20sought-20to-20define-20the-20state-20of-20mitochondrial-20metabolism-20in-20PH-2DFibs.-20In-20PH-2DFibs-20pyruvate-20dehydrogenase-20was-20markedly-20inhibited,-20resulting-20in-20metabolism-20of-20pyruvate-20to-20lactate,-20thus-20consistent-20with-20a-20Warburg-2Dlike-20phenotype.-20In-20addition,-20mitochondrial-20bioenergetics-20were-20suppressed-20and-20mitochondrial-20fragmentation-20was-20increased-20in-20PH-2DFibs.-20Most-20importantly,-20Complex-20I-20activity-20was-20substantially-20decreased-20which-20was-20associated-20with-20downregulation-20of-20the-20accessory-20subunit-20NDUFS4.-20Due-20to-20less-20efficient-20ATP-20synthesis-20mitochondria-20were-20hyperpolarized-20and-20mitochondrial-20superoxide-20production-20was-20increased.-20This-20pro-2Doxidative-20status-20was-20further-20augmented-20by-20simultaneous-20induction-20of-20cytosolic-20NADPH-20oxidase-204.-20While-20acute-20and-20chronic-20exposure-20to-20hypoxia-20of-20adventitial-20fibroblasts-20from-20healthy-20control-20vessels-20induced-20increased-20glycolysis,-20it-20did-20not-20induce-20Complex-20I-20deficiency-20as-20observed-20in-20PH-2DFibs.-20This-20suggests-20that-20hypoxia-20alone-20is-20insufficient-20to-20induce-20NDUFS4-20downregulation-20and-20constitutive-20abnormalities-20in-20Complex-20I.-20In-20conclusion,-20our-20study-20provides-20evidence-20that-20in-20the-20pathogenesis-20of-20vascular-20remodeling-20in-20PH,-20alterations-20in-20fibroblast-20mitochondrial-20metabolism-20drive-20distinct-20changes-20in-20cellular-20behavior,-20which-20potentially-20occur-20independently-20of-20hypoxia." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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