Estrogen treatment abrogates neointima formation in human C-reactive protein transgenic mice

Objective - Previously we established that the vascular injury response was attenuated in ovariectomized wild-type rodents treated with 17 beta-estradiol (E-2). 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 E-2 modulates vascular injury in the CRPtg mouse. Methods and Results - Intact (INT) or ovariectomized (OVX) CRPtg and NTG, treated with E-2 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 E-2. 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 E-2 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. E-2 reduces both neointima formation and neointimal expression of human CRP, suggesting that E-2 is vasoprotective.