David N. Cornfield

Publication Details

  • Hypoxia-inducible factor-1a in pulmonary artery smooth muscle cells lowers vascular tone by decreasing Myosin light chain phosphorylation. Circulation research Kim, Y., Barnes, E. A., Alvira, C. M., Ying, L., Reddy, S., Cornfield, D. N. 2013; 112 (9): 1230-1233


    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. Methods andMice 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.

    View details for DOI 10.1161/CIRCRESAHA.112.300646

    View details for PubMedID 23513056

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