Hypoxia-inducible factor-1? in pulmonary artery smooth muscle cells lowers vascular tone by decreasing myosin light chain phosphorylation.

ABSTRACT: Hypoxia-inducible factor-1? (HIF-1?), an oxygen (O2)-sensitive transcription factor, mediates transcriptional responses to low-O2 tension states. Although acute hypoxia causes pulmonary vasoconstriction and chronic hypoxia can cause vascular remodeling and pulmonary hypertension, conflicting data exist on the role of HIF-1? in modulating pulmonary vascular tone.To investigate the role of smooth muscle cell (SMC)-specific HIF-1? in regulating pulmonary vascular tone.Mice with an SMC-specific deletion of HIF-1? (SM22?-HIF-1?(-/-)) were created to test the hypothesis that pulmonary artery SMC (PASMC) HIF-1? modulates pulmonary vascular tone and the response to hypoxia. SM22?-HIF-1?(-/-) mice exhibited significantly higher right ventricular systolic pressure compared with wild-type littermates under normoxia and with exposure to either acute or chronic hypoxia in the absence of histological evidence of accentuated vascular remodeling. Moreover, myosin light chain phosphorylation, a determinant of SMC tone, was higher in PASMCs isolated from SM22?-HIF-1?(-/-) mice compared with wild-type PASMCs, during both normoxia and after acute hypoxia. Further, overexpression of HIF-1? decreased myosin light chain phosphorylation in HIF-1?-null SMCs.In both normoxia and hypoxia, PASMC HIF-1? maintains low pulmonary vascular tone by decreasing myosin light chain phosphorylation. Compromised PASMC HIF-1? expression may contribute to the heightened vasoconstriction that characterizes pulmonary hypertension.

SUBMITTER: Kim YM 

PROVIDER: S-EPMC4005857 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature