on July 28, 2005
Published online before print July 28, 2005, doi: 10.1161/01.ATV.0000179602.85797.3f
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Submitted on April 1, 2005
Accepted on July 13, 2005
Estrogen Treatment Abrogates Neointima Formation in Human C-Reactive Protein Transgenic Mice
Dajun Wang ;
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.
* To whom correspondence should be addressed. 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 17
-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.
Key words: C-reactive protein • estrogen • hormone replacement therapy • cardiovascular disease • inflammation
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