| http://purl.uniprot.org/citations/37847687 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37847687 | http://www.w3.org/2000/01/rdf-schema#comment | "Pulmonary arterial hypertension (PAH) is a disease characterized by increased vasoconstriction and vascular remodeling. Pulmonary artery smooth muscle cells (PASMCs) highly express the transcription factor hypoxia-inducible factor-1α (HIF-1α), yet the role of PASMC HIF-1α in the development of PAH remains controversial. To study the role of SMC HIF-1α in the pulmonary vascular response to acute and chronic hypoxia, we used a gain-of-function strategy to stabilize HIF-1α in PASMC by generating mice lacking prolyl hydroxylase domain (PHD) 1 and 2 in SM22α-expressing cells. This strategy increased HIF-1α expression and transcriptional activity under conditions of normoxia and hypoxia. Acute hypoxia increased right ventricular systolic pressure (RVSP) in control, but not in SM22α-PHD1/2-/- mice. Chronic hypoxia increased RVSP and vascular remodeling more in control SM22α-PHD1/2+/+ than in SM22α-PHD1/2-/- mice. In vitro studies demonstrated increased contractility and myosin light chain phosphorylation in isolated PHD1/2+/+ compared with PHD1/2-/- PASMC under both normoxic and hypoxic conditions. After chronic hypoxia, there was more p27 and less vascular remodeling in SM22α-PHD1/2-/- compared with SM22α-PHD1/2+/+ mice. Hypoxia increased p27 in PASMC isolated from control patients, but not in cells from patients with idiopathic pulmonary arterial hypertension (IPAH). These findings highlight an SM22α-expressing cell-specific role for HIF-1α in the inhibition of pulmonary vasoconstriction and vascular remodeling. Modulating HIF-1α expression in PASMC may represent a promising preventative and therapeutic strategy for patients with PAH.NEW & NOTEWORTHY In a mouse model wherein hypoxia-inducible factor 1 alpha (HIF-1α) is stabilized in vascular smooth muscle cells, we found that HIF-1α regulates vasoconstriction by limiting phosphorylation of myosin light chain and regulates vascular remodeling through p27 induction. These findings highlight a cell-specific role for HIF-1α in the inhibition of pulmonary vasoconstriction and vascular remodeling."xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajplung.00428.2022"xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/author | "Ito R."xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/author | "Che X."xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/author | "Barnes E.A."xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/author | "Cornfield D.N."xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/author | "Alvira C.M."xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/name | "Am J Physiol Lung Cell Mol Physiol"xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/pages | "L741-L755"xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/title | "Loss of prolyl hydroxylase 1 and 2 in SM22alpha-expressing cells prevents Hypoxia-Induced pulmonary hypertension."xsd:string |
| http://purl.uniprot.org/citations/37847687 | http://purl.uniprot.org/core/volume | "325"xsd:string |
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