Primary Pulmonary Hypertension Is Associated With Reduced Pulmonary Vascular Expression of Type II Bone Morphogenetic Protein Receptor
By C. Atkinson, S. Stewart, P. Upton, R. Machado, J. Thomson, R. Trembath, N. Morrell. Circulation, 2002
696 citations recorded by the source corpus.
Background—Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming growth factor-&bgr; (TGF-&bgr;) superfamily, underlie many familial and sporadic cases of primary pulmonary hypertension (PPH). Methods and Results—Because the sites of expression of BMPR-II in the normal and hypertensive lung are unknown, we studied the cellular localization of BMPR-II and the related type I and II receptors for TGF-&bgr; by immunohistochemistry in lung sections from patients undergoing heart-lung transplantation for PPH (n=11, including 3 familial cases) or secondary pulmonary hypertension (n=6) and from unused donor lungs (n=4). In situ hybridization was performed for BMPR-II mRNA. Patients were screened for the presence of mutations in BMPR2. In normal lungs, BMPR-II expression was prominent on vascular endothelium, with minimal expression in airway and arterial smooth muscle. In pulmonary hypertension cases, the intensity of BMPR-II immunostaining varied between lesions but involved endothelial and myofibroblast components. Image analysis confirmed that expression of BMPR-II was markedly reduced in the peripheral lung of PPH patients, especially in those harboring heterozygous BMPR2 mutations. A less marked reduction was also observed in patients with secondary pulmonary hypertension. In contrast, there was no difference in level of staining for TGF-&bgr;RII or the endothelial marker CD31. Conclusions—The cellular localization of BMPR-II is consistent with a role in the formation of pulmonary vascular lesions in PPH, and reduced BMPR-II expression may contribute to the process of vascular obliteration in severe pulmonary hypertension.
Subfields: Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/1c2b5badd56db99ac30ca88c824639f02a262039
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In Pulmonary and Respiratory Medicine
Citations in the corpus
- Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. (2009, background): “Based on a report showing that BMPR2 expression is almost completely absent in the endothelial cells of plexiform or concentric vascular lesions of FPAH patients harboring heterozygous BMPR2 mutations (6, 97), studies were carried out by Hong et al.”
- Molecular pathogenesis of pulmonary arterial hypertension. (2008, background): “most IPAH patients have reduced BMPR2 protein expression, as do, to some extent, patients with PAH associated with other conditions (33).”
- Cellular and molecular pathobiology of pulmonary arterial hypertension. (2004, background): “Lung BMPR-II protein expression is dramatically reduced in patients harboring an underlying BMPR2 mutation predicted to cause truncation of the protein ( 42 ).”
- Genetics and genomics of pulmonary arterial hypertension. (2013, background): “Another candidate for epigenetic study is BMPR2, with significantly down-regulated expression in many PAH lungs, even in the absence of a germline mutation (78,100).”
- Cellular and Molecular Basis of Pulmonary Arterial Hypertension (2009, background): “Moreover, studies using isolated PASMCs and PAs from monocrotaline-exposed hypertensive rats revealed that suppression of tenascin-C using an antisense approach induces SMC apoptosis and regression of pulmonary vascular lesions (114).”