This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One of the signaling systems critical in protection against the development of pulmonary hypertension is that through the bone morphogenetic protein receptor 2 (BMPRII). Mutations that lead to loss of signaling through BMPRII receptors are found in 70% of cases of familial pulmonary hypertension. Preliminary data from our lab has indicated that the multi-functional adapter protein beta-arrestin (1 and 2) binds and regulates signaling by BMPRII. To better understand the functional consequences of this altered signaling, we have subjected wild type, beta-arrestin1 and beta-arrestin2 KO animals to conditions of chronic hypoxia (simulated altitude) that lead to the development of pulmonary hypertension. In preliminary studies, we have demonstrated that beta-arrestin KO mice show altered susceptibility to the development of pulmonary hypertension induced by chronic hypoxia as assessed by differences in right ventricular hypertrophy (mass of RV / mass of LV + septum). We now plan on better characterizing these differences by more detailed analysis of cardiac and pulmonary morphology by microCT. We hope that studies by microCT will allow a detailed analysis of RV morphology, stroke volume (and cardiac output) and of changes in the pulmonary vasculature (loss of small vessels resulting in """"""""pruning""""""""). In concert with our preliminary data and data from cardiac catheterization, we will be able to comprehensively characterize changes in the development of pulmonary hypertension in the beta-arrestin KO mice and correlate this with changes in the BMPRII signaling.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR005959-21
Application #
8171621
Study Section
Special Emphasis Panel (ZRG1-SBIB-P (40))
Project Start
2010-07-01
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
21
Fiscal Year
2010
Total Cost
$10,920
Indirect Cost
Name
Duke University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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