Abstract 14875: Estrogen-Induced Vasoprotection is Preserved After Prolonged Estrogen Deprivation
Introduction: 17β-Estradiol (E2) offers cardiovascular protection in young female animals and peri-menopausal women. Clinical trials carried out in older women deprived of E2 for many years have shown harm or no cardiovascular benefit. We have recently demonstrated that E2 attenuates C-reactive protein (CRP)-driven inflammatory response in vascular smooth muscle cells and macrophages derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice (CRPtg).
Hypothesis: After prolonged E2 deprivation, E2 will not attenuate neointimal response to vascular injury.
Methods and Results: C57BL/6 non-transgenic (NTG) and CRPtg (10 wk old) mice underwent ovariectomy and then received vehicle (veh), uninterrupted E2 for 97 days (E2), or veh for 90 days followed by E2 for 7 days (E2, deprivation) delivered using subcutaneous pellets. Mice were then subjected to right common carotid artery ligation. At 28 days after injury, the carotid arteries were harvested, fixed, sectioned, stained, and subjected to computer-assisted morphometric analysis to assess the extent of the injury response. In veh treated mice, neointima formation was exaggerated in CRPtg compared to NTG (Figure). E2 treatment, whether continuous or after prolonged deprivation, was associated with greatly diminished neointima formation in both genotypes (2-way ANOVA interaction not significant). Importantly, the extent of neointima formation was not different between the two E2-treated groups (E2 vs. E2, deprivation).
Conclusions: In mice, E2-induced vasoprotection abolishes CRP-mediated vascular injury and this effect is preserved even after prolonged E2 deprivation. In combination with our previous finding that the vasoprotective effects of E2 are age-dependent, the current data suggest that the lack of benefit associated with E2 seen in clinical trials is associated with advanced age rather than prolonged E2 deprivation.
Author Disclosures: F.G. Hage: None. D. Xing: None. Y. Guo: None. C. Colon: None. A.J. Szalai: None. Y. Chen: None. S. Oparil: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.