A series of epidemiological studies have revealed a consistent association of circulating C-reactive protein (CRP) levels with risk of ischemic cardiovascular disease among apparently healthy individuals. CRP may have great clinical values on cardiovascular risk assessment and early prevention, and its underlying pathological mechanisms may provide novel therapeutic strategies. However, further application of CRP on clinical practice is hampered by a key issue -- whether CRP is a direct risk mediator for cardiovascular disease or it is merely an innocent bystander. Due to the inherent limitations of in vitro experiments on the CRP study, in vivo study on suitable animal models has become essential to address this issue. We propose to create a transgenic rat model that over-expresses the human CRP gene in the liver. Our selection of rats rather than mice is based on recent observations from the CRP transgenic mice and the CRP intraperitoneally injected rats. Compared with intraperitoneal injection, transgenic over-expression offers a long-term and stable elevation of human CRP in the rats. Specifically, we will (1) generate ALB-hCRP transgenic rats driven by the albumin enhancer/promoter;and (2) perform a pilot phenotype characterization of ALB-hCRP transgenic rats on systematic inflammation, endothelial activation and vascular lesion formation. We anticipate that this animal model will provide an in vivo platform for exploring the CRP pathological role in the development of cardiovascular disease. It will also provide a platform for screening and testing new preventive and therapeutic strategies for cardiovascular disease based on new understandings of the CRP biology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Pilot Research Project (SC2)
Project #
5SC2HL095098-03
Application #
7867962
Study Section
Special Emphasis Panel (ZGM1-MBRS-0 (SC))
Program Officer
Mcdonald, Cheryl
Project Start
2008-08-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2010
Total Cost
$105,000
Indirect Cost
Name
Morehouse School of Medicine
Department
Type
Organized Research Units
DUNS #
102005451
City
Atlanta
State
GA
Country
United States
Zip Code
30310
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