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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2094.)
© 2005 American Heart Association, Inc.

Vascular Biology

Estrogen Treatment Abrogates Neointima Formation in Human C-Reactive Protein Transgenic Mice

Dajun Wang; Suzanne Oparil; Yiu-Fai Chen; Mark A. McCrory; Gregory A. Skibinski; Wenguang Feng; Alexander J. Szalai

From the Vascular Biology and Hypertension Program, Division of Cardiovascular Disease (D.W., S.O., Y.-F.C., W.F.) and the Division of Clinical Immunology and Rheumatology (M.A.M., G.A.S., A.J.S.), Department of Medicine, the University of Alabama at Birmingham.

Correspondence to Alexander J. Szalai, PhD, the University of Alabama at Birmingham, Division of Clinical Immunology and Rheumatology, THT 437B, 1530 3rd Avenue South, Birmingham, Alabama 35294-0006. E-mail Alex.Szalai{at}ccc.uab.edu

Objective— Previously we established that the vascular injury response was attenuated in ovariectomized wild-type rodents treated with 17ß-estradiol (E₂). We also showed that the response to acute vascular injury in transgenic mice expressing human C-reactive protein (CRPtg) is exaggerated compared with their nontransgenic (NTG) counterparts. Herein we tested the hypothesis that E₂ modulates vascular injury in the CRPtg mouse.

Methods and Results— Intact (INT) or ovariectomized (OVX) CRPtg and NTG, treated with E₂ or vehicle, had their right common carotid artery ligated. Resultant neointima formation was exaggerated in CRPtg compared with NTG, whether INT or OVX, but was prevented in both genotypes by E₂. Expression of human CRP protein (immunohistochemical analysis) and mRNA (laser microdissection followed by real-time quantitative RT-PCR) was detected in the neointima of OVX CRPtg and was greatly diminished by E₂ treatment. CRP was not detected in uninjured arteries or in the media of injured arteries, and blood CRP level was consistently low.

Conclusions— The exaggerated response to vascular injury in CRPtg is associated with increased neointimal expression of human CRP. E₂ reduces both neointima formation and neointimal expression of human CRP, suggesting that E₂ is vasoprotective.

We tested whether estrogen could modulate the exaggerated vascular response to injury seen in C-reactive protein (CRP) transgenic mice. Estrogen treatment reduced carotid artery ligation–induced expression of CRP (protein and mRNA) in the neointima, and lessened CRP-mediated exacerbation of injury. These data suggest that estrogen is vasoprotective.

Key Words: C-reactive protein • estrogen • hormone replacement therapy • cardiovascular disease • inflammation

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