Aged rats lose vasoprotective and anti-inflammatory actions of estrogen in injured arteries

Abstract

Objective: 17β-Estradiol (E₂) negatively modulates neointima formation, leukocyte infiltration, and proinflammatory mediator expression after vascular injury in young (10-wk-old) ovariectomized (OVX) rats. Trials of E₂ in elderly postmenopausal women have not confirmed a vasoprotective effect. This study tested the hypothesis that responsiveness to E₂ is lost in injured arteries of aged (12-mo-old) OVX rats. Design: E₂- or vehicle-treated OVX rats underwent balloon injury of the carotid artery and were killed after 2 weeks for morphometric examination of arteries, after 24 hours for assessment of leukocyte infiltration, and after 2 hours for quantification of proinflammatory mediator mRNA expression. Results: Neointima formation was significantly reduced in aged compared with young vehicle-treated rats. E₂ treatment had directionally opposite effects on intima/media ratios in aged (+75%) and young (−40%) rats. Injury induced increases in infiltrating total leukocytes, neutrophils, monocytes/macrophages, and expression of proinflammatory mediators in arteries of aged rats; E₂ had no effect on these inflammatory responses to injury. Estrogen receptor α and β protein expression were similar in carotid arteries of young and aged rats on immunofluorescence testing. Conclusions: Aged OVX rats lose the vasoprotective and anti-inflammatory responses to exogenous E₂ seen in younger animals. These results may be relevant to the lack of vasoprotection observed in outcome trials of estrogen therapy in postmenopausal women.