Mark de Caestecker
Associate Professor of Medicine
Last active: 10/23/2018

Increased susceptibility to hypoxic pulmonary hypertension in Bmpr2 mutant mice is associated with endothelial dysfunction in the pulmonary vasculature.

Frank DB, Lowery J, Anderson L, Brink M, Reese J, de Caestecker M
Am J Physiol Lung Cell Mol Physiol. 2008 294 (1): L98-109

PMID: 18024717 · DOI:10.1152/ajplung.00034.2007

Patients with familial pulmonary arterial hypertension inherit heterozygous mutations of the type 2 bone morphogenetic protein (BMP) receptor BMPR2. To explore the cellular mechanisms of this disease, we evaluated the pulmonary vascular responses to chronic hypoxia in mice carrying heterozygous hypomorphic Bmpr2 mutations (Bmpr2 delta Ex2/+). These mice develop more severe pulmonary hypertension after prolonged exposure to hypoxia without an associated increase in pulmonary vascular remodeling or proliferation compared with wild-type mice. This is associated with defective endothelial-dependent vasodilatation and enhanced vasoconstriction in isolated intrapulmonary artery preparations. In addition, there is a selective decrease in hypoxia-induced, BMP-dependent, endothelial nitric oxide synthase expression and Smad signaling in the intact lungs and in cultured pulmonary microvascular endothelial cells from Bmpr2 delta Ex2/+ mutant mice. These findings indicate that the pulmonary endothelium is a target of abnormal BMP signaling in Bmpr2 delta Ex2/+ mutant mice and suggest that endothelial dysfunction contributes to their increased susceptibility to hypoxic pulmonary hypertension.

MeSH Terms (12)

Animals Bone Morphogenetic Protein Receptors, Type II Endothelium, Vascular Genetic Predisposition to Disease Hydrogen-Ion Concentration Hypertension, Pulmonary Hypoxia Mice Mice, Knockout Mice, Mutant Strains Mutation Pulmonary Circulation

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