Aged rats lose vasoprotective and anti-inflammatory actions of estrogen in injured arteries.
OBJECTIVE
17beta-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.


METHODS
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 alpha and beta 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.
Miller
Andrew P
AP
Department of Medicine, University of Alabama at Birmingham 35294-0007, USA. apmiller@uab.edu
Xing
Dongqi
D
Feng
Wenguang
W
Fintel
Marion
M
Chen
Yiu-Fai
YF
Oparil
Suzanne
S
D000375:Aging; D000818:Animals; D020212:Carotid Artery Injuries / Q000473:pathology / Q000517:prevention & control*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018836:Inflammation Mediators; D004958:Estradiol