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Abstract

17β-estradiol (E2) negatively modulates the neointimal response to vascular injury in young (10 wk old) ovariectomized (OVX) rats, at least in part, by limiting inflammation early in the injury response. Trials in elderly women treated with hormone therapy after many hormone-free years have not confirmed a vasoprotective effect.

The beneficial effects of E2 on the vascular injury response are blunted in aged (10-14 mo old) rats.

In morphometric studies, young and aged OVX rats were treated with vehicle (V) or E2, sacrificed 2 wks after balloon injury of the right common carotid artery, and cross-sectional neointimal areas and intima-to-media ratios were determined. In studies of early vascular inflammation, 24 hrs post-injury, rats were euthanized and carotid arteries (injured and control) were analyzed for inflammatory cells by flow cytometry.

In young rats, E2 was associated with a significant 40% reduction in the neointima response, confirming our previous results. In contrast, compared to aged V controls, intimal areas and intima-to-media ratios were significantly greater in aged rats treated with E2. Neointima formation was significantly reduced in aged V compared to young V rats. Serum E2 was within the physiologic range in both E2 treated young and aged rats. While flow cytometry of the injured young rat arteries demonstrated that E2 reduced the granulocyte and monocyte/macrophage populations of injured vessels by ∼50% and increased T-lymphocytes, no difference was observed between injured vessels from V and E2 treated aged animals in infiltrating leukocyte subtypes.

Aged rats subjected to a period of surgically induced E2 deprivation lose the vasoprotective response to exogenous E2 in the setting of acute endoluminal vascular injury. Further study is needed to test whether a similar lack of E2 responsiveness occurs at the vascular level in aging postmenopausal women. See Table 1.

SubgroupSerum 17β-estradiol (pg/ml)Neointima Area (mm2)Intima: Media Ratio
Young OVX + V (n = 5)14.6 ± 4.10.13 ± 0.011.17 ± 0.18
Young OVX + E2 (n = 5)51.2 ± 10.7;*0.09 ± 0.010.71 ± 0.10;*
Aged OVX + V (n = 11)18.7 ± 5.70.06 ± 0.01;#0.35 ± 0.04;#
Aged OVX + E2 (n = 18)50.3 ± 12.5;*0.11 ± 0.01;*0.62 ± 0.06;*
SubgroupSerum 17β-estradiol (pg/ml)Neointima Area (mm2)Intima: Media Ratio
Young OVX + V (n = 5)14.6 ± 4.10.13 ± 0.011.17 ± 0.18
Young OVX + E2 (n = 5)51.2 ± 10.7;*0.09 ± 0.010.71 ± 0.10;*
Aged OVX + V (n = 11)18.7 ± 5.70.06 ± 0.01;#0.35 ± 0.04;#
Aged OVX + E2 (n = 18)50.3 ± 12.5;*0.11 ± 0.01;*0.62 ± 0.06;*

Values are mean ± SEM, ;*p < 0.05 vs respective V, ;#p < 0.05 vs respective Young.

SubgroupSerum 17β-estradiol (pg/ml)Neointima Area (mm2)Intima: Media Ratio
Young OVX + V (n = 5)14.6 ± 4.10.13 ± 0.011.17 ± 0.18
Young OVX + E2 (n = 5)51.2 ± 10.7;*0.09 ± 0.010.71 ± 0.10;*
Aged OVX + V (n = 11)18.7 ± 5.70.06 ± 0.01;#0.35 ± 0.04;#
Aged OVX + E2 (n = 18)50.3 ± 12.5;*0.11 ± 0.01;*0.62 ± 0.06;*
SubgroupSerum 17β-estradiol (pg/ml)Neointima Area (mm2)Intima: Media Ratio
Young OVX + V (n = 5)14.6 ± 4.10.13 ± 0.011.17 ± 0.18
Young OVX + E2 (n = 5)51.2 ± 10.7;*0.09 ± 0.010.71 ± 0.10;*
Aged OVX + V (n = 11)18.7 ± 5.70.06 ± 0.01;#0.35 ± 0.04;#
Aged OVX + E2 (n = 18)50.3 ± 12.5;*0.11 ± 0.01;*0.62 ± 0.06;*

Values are mean ± SEM, ;*p < 0.05 vs respective V, ;#p < 0.05 vs respective Young.

Hormones, Aging, Restenosis
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© American Journal of Hypertension, Ltd. 2004
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