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 17beta-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.


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.
Wang
Dajun
D
Division of Cardiovascular Disease, University of Alabama, Birmingham, Alabama 35294-0006, USA.
Oparil
Suzanne
S
Chen
Yiu-Fai
YF
McCrory
Mark A
MA
Skibinski
Gregory A
GA
Feng
Wenguang
W
Szalai
Alexander J
AJ
D000208:Acute Disease; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000473:pathology / Q000517:prevention & control*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010052:Ovariectomy; D000683:Serum Amyloid P-Component / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D000683:Serum Amyloid P-Component; D004958:Estradiol; D002097:C-Reactive Protein