期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 287, 期 6, 页码 L1241-L1247出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00239.2004
关键词
pulmonary vasculature; smooth muscle cells; bone morphogenetic protein; hypoxia
资金
- NHLBI NIH HHS [HL-42397, HL-71987, HL-74352] Funding Source: Medline
- NICHD NIH HHS [HD-35286] Funding Source: Medline
Heterozygous mutations of the bone morphogenetic protein type II receptor (BMPR-II) gene have been identified in patients with primary pulmonary hypertension. The mechanisms by which these mutations contribute to the pathogenesis of primary pulmonary hypertension are not fully elucidated. To assess the impact of a heterozygous mutation of the BMPR-II gene on the pulmonary vasculature, we studied mice carrying a mutant BMPR-II allele lacking exons 4 and 5 (BMPR-II+/- mice). BMPR-II+/- mice had increased mean pulmonary arterial pressure and pulmonary vascular resistance compared with their wild-type littermates. Histological analyses revealed that the wall thickness of muscularized pulmonary arteries (<100 μm in diameter) and the number of alveolar-capillary units were greater in BMPR-II+/- than in wild-type mice. Breathing 11% oxygen for 3 wk increased mean pulmonary arterial pressure, pulmonary vascular resistance, and hemoglobin concentration to similar levels in BMPR-II+/- and wild-type mice, but the degree of muscularization of small pulmonary arteries and formation of alveolar-capillary units were reduced in BMPR-II+/- mice. Our results suggest that, in mice, mutation of one copy of the BMPR-II gene causes pulmonary hypertension but impairs the ability of the pulmonary vasculature to remodel in response to prolonged hypoxic breathing.
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