This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The proposed research is designed to determine the prevalenc and risk factors of pulmonry hypertension (PHTN) in children and adolescents with sickle cell disease (SCD), and to determine the role of the hypoxic response in it s pathogenesis. The present proposal is based on three postulates. First, the problem of SCD-associated PHTN may begin during childhood and adolescence. Second, the pathogenesis of SCD-associated PHTN may include not only the effects of nitric oxide scavenging in a chronic hemolytic disorder, but also the consequences of chronic hypoxia related to severe anemia and to repeated vasoocclusive episodes. PHTN is a complication of conditions marked by chronic hypoxia, and aslo a complication of Chuvash polycythemia (CP), a congenital disorder of oxygen sensing in which the hypoxic response is constitutively up regulated in the absence of hypoxia. Third, we postulate that the pathophysiology of SCD-associated PHTN may be elucidated by comparing proliferative vascular responses medicated by HIF and by nitric oxide scavenging in patients with SCD and CP according to the presence or absence of pulmonary hypertension. Based on a comparison of the clinical and pathophysiologic features of SCD and CP, we hypothesize that, in addition to increased nitric oxide-scavenging, altered expression of a gene or genes regulated by hypoxia inducible factor (HIF) is central to the pathophysiology of PHTN in both SCD and CP.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR010284-13
Application #
7719000
Study Section
Special Emphasis Panel (ZRR1-CR-8 (02))
Project Start
2008-03-01
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
13
Fiscal Year
2008
Total Cost
$143,912
Indirect Cost
Name
Howard University
Department
Type
Schools of Medicine
DUNS #
056282296
City
Washington
State
DC
Country
United States
Zip Code
20059
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