Bone Morphogenetic Protein Receptor 2 Mutations in Adults and Children With Idiopathic Pulmonary Arterial Hypertension

CHEST Journal ◽  
2005 ◽  
Vol 128 (6) ◽  
pp. 618S ◽  
Author(s):  
Kari E. Roberts ◽  
Robyn J. Barst ◽  
Jude J. McElroy ◽  
Allison Widlitz ◽  
Kiran Chada ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bone Morphogenetic Protein ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Bone Morphogenetic Protein Receptor ◽  
Protein Receptor ◽  
Morphogenetic Protein ◽  
Adults And Children ◽  
Pulmonary Arterial

Overexpression of human bone morphogenetic protein receptor 2 does not ameliorate monocrotaline pulmonary arterial hypertension

2007 ◽  
Vol 292 (4) ◽  
pp. L872-L878 ◽  
Author(s):  
M. Sean McMurtry ◽  
Rohit Moudgil ◽  
Kyoko Hashimoto ◽  
Sandra Bonnet ◽  
Evangelos D. Michelakis ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Fluorescence Microscopy ◽  
Arterial Hypertension ◽  
Bone Morphogenetic Protein ◽  
Transgene Expression ◽  
Rt Pcr ◽  
Bone Morphogenetic Protein Receptor ◽  
Protein Receptor ◽  
Morphogenetic Protein ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is associated with mutations of bone morphogenetic protein receptor 2 (BMPR2), and BMPR2 expression decreases with the development of experimental PAH. Decreased BMPR2 expression and impaired intracellular BMP signaling in pulmonary artery (PA) smooth muscle cells (PASMC) suppresses apoptosis and promotes proliferation, thereby contributing to the pathogenesis of PAH. We hypothesized that overexpression of BMPR2 in resistance PAs would ameliorate established monocrotaline PAH. Human BMPR2 was inserted into a serotype 5 adenovirus with a green fluorescent protein (GFP) reporter. Dose-dependent transgene expression was confirmed in PASMC using fluorescence microscopy, quantitative RT-PCR, and immunoblots. PAH was induced by injecting Sprague-Dawley rats with monocrotaline (60 mg/kg ip) or saline. On day 14, post-monocrotaline (MCT) rats received 5 × 109 plaque-forming units of either Ad-human BMPR2 (Ad-hBMPR2) or Ad-GFP. Transgene expression was confirmed by fluorescence microscopy, quantitative RT-PCR of whole lung samples, and laser-capture microdissected resistance PAs. Invasive hemodynamic and echocardiographic end points of pulmonary hypertension were assessed on day 24. Endogenous BMPR2 mRNA levels were greatest in resistance PAs, and expression declined with MCT PAH. Despite robust hBMPR2 expression in all lung lobes and within resistance PAs of treated rats, hBMPR2 did not lower mean PA pressure, pulmonary vascular resistance index, right ventricular hypertrophy, or remodeling of resistance PAs. Nebulized intratracheal adenoviral gene therapy with hBMPR2 reliably distributed hBMPR2 to resistance PAs but did not ameliorate PAH. Depressed BMPR2 expression may be a marker of PAH but is not central to the pathogenesis of this model of PAH.

scholarly journals Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension

Circulation ◽  
2016 ◽  
Vol 133 (18) ◽  
pp. 1747-1760 ◽  
Author(s):  
Cathelijne E. van der Bruggen ◽  
Chris M. Happé ◽  
Peter Dorfmüller ◽  
Pia Trip ◽  
Onno A. Spruijt ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bone Morphogenetic Protein ◽  
Receptor Type ◽  
Bone Morphogenetic Protein Receptor ◽  
Protein Receptor ◽  
Morphogenetic Protein ◽  
Pulmonary Arterial
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