| First Author | Kim YM | Year | 2013 |
| Journal | Circ Res | Volume | 112 |
| Issue | 9 | Pages | 1230-3 |
| PubMed ID | 23513056 | Mgi Jnum | J:213312 |
| Mgi Id | MGI:5584076 | Doi | 10.1161/CIRCRESAHA.112.300646 |
| Citation | Kim YM, et al. (2013) Hypoxia-inducible factor-1alpha in pulmonary artery smooth muscle cells lowers vascular tone by decreasing myosin light chain phosphorylation. Circ Res 112(9):1230-3 |
| abstractText | RATIONALE: Hypoxia-inducible factor-1alpha (HIF-1alpha), 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-1alpha in modulating pulmonary vascular tone. OBJECTIVE: To investigate the role of smooth muscle cell (SMC)-specific HIF-1alpha in regulating pulmonary vascular tone. METHODS AND RESULTS: Mice with an SMC-specific deletion of HIF-1alpha (SM22alpha-HIF-1alpha(-/-)) were created to test the hypothesis that pulmonary artery SMC (PASMC) HIF-1alpha modulates pulmonary vascular tone and the response to hypoxia. SM22alpha-HIF-1alpha(-/-) 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 SM22alpha-HIF-1alpha(-/-) mice compared with wild-type PASMCs, during both normoxia and after acute hypoxia. Further, overexpression of HIF-1alpha decreased myosin light chain phosphorylation in HIF-1alpha-null SMCs. CONCLUSIONS: In both normoxia and hypoxia, PASMC HIF-1alpha maintains low pulmonary vascular tone by decreasing myosin light chain phosphorylation. Compromised PASMC HIF-1alpha expression may contribute to the heightened vasoconstriction that characterizes pulmonary hypertension. |
