17β-estradiol, gender independently, reduces atheroma development but not neointimal proliferation after balloon injury in the rabbit aorta

Finking, Gerald; Krauß, Norbert; Römer, Simone; Eckert, Stephan; Lenz, Christina; Kamenz, Joachim; Menke, André; Brehme, Ute; Hombach, Vinzenz; Hanke, Hartmut

doi:10.1016/s0021-9150(00)00446-9

Cited by 13 publications

(5 citation statements)

References 61 publications

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“…Similar to the findings in primates, administration of estradiol prior and during, but not seven days after, balloon injury resulted in inhibition of neointima formation in rats [53]. Delayed delivery also failed to prevent neointima formation in rabbits [54].…”

Section: Role Of Timing Of Hrtsupporting

confidence: 76%

Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen

Dubey

Imthurn

Barton

et al. 2005

Cardiovascular Research

212

170

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Premenopausal women have a lower risk for cardiovascular events, and mortality due to coronary vascular disease (CVD) in premenopausal women is rare. These facts suggest that endogenous estrogens, such as estradiol, protect the cardiovascular system, and several observational studies and a few small clinical studies conducted in healthy and younger postmenopausal women support this hypothesis. In contrast, two large randomized clinical trials (RCTs), using conjugated equine estrogens and conducted in older women with established CVD or without overt CVD, failed to demonstrate protection against CVD by exogenous estrogens. These divergent findings have resulted in confusion with regard to the association between estrogen deficiency and CVD in postmenopausal women. In order to reconcile these contradictory findings, it is necessary to examine the pathophysiology associated with age-dependent changes within the vessel wall and to compare the pharmacology of different types of estrogens. Understanding age-dependent changes in vascular pathology and the pharmacology of different estrogens may facilitate the development of therapeutic strategies for hormone replacement therapy (HRT) that would be effective in delaying vascular remodeling leading to CVD following menopause. In this review we provide an overview of the impact of menopause and estrogen deficiency on vascular remodeling and emphasize the importance of timing and type of estrogen to achieve maximum benefits with regard to reducing the risk of CVD.

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Section: Role Of Timing Of Hrtsupporting

confidence: 76%

Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen

Dubey

Imthurn

Barton

et al. 2005

Cardiovascular Research

212

170

View full text Add to dashboard Cite

show abstract

“…Several studies have shown that estrogen treatment may have beneficial effects on the cardiovascular system by reducing postinjury neointimal formation in animal carotid arteries 20 and by improving some aspects of endothelial function in postmenopausal women. 21 We have previously demonstrated that a local delivery of 17␤E on a porcine coronary angioplasty reduces the degree of restenosis by up to 50% and improves the reendothelialization, eNOS expression, and vascular healing.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Regulation of Endothelial and Smooth Muscle Cell Migration and Proliferation

Geraldes

Sirois

Bernatchez

et al. 2002

ATVB

105

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Objective-Restenosis is a major limitation of percutaneous coronary intervention. Migration and proliferation of vascular cells remain a cornerstone in neointimal formation. The cardioprotection of estrogen is well recognized, but the intracellular mechanisms related to these beneficial effects are not completely understood. Methods and Results-We investigated the effects of 17␤-estradiol (17␤E) on mitogen-activated protein kinase (MAPK) activity and the migration and proliferation of porcine aortic endothelial cells (PAECs) and porcine smooth muscle cells (PSMCs). Treatment with 17␤E (10 Ϫ8 mol/L) abrogated p38 and p42/44 MAPK phosphorylation mediated by platelet-derived growth factor-BB as well as the migration and proliferation of PSMCs. In contrast, treatment with 17␤E (10 Ϫ8 mol/L) induced the phosphorylation of p38 and p42/44 MAPK and the migration and proliferation of PAECs. Interestingly, the effects of 17␤E on PSMCs and PAECs were reversed by selective estrogen receptor antagonists (tamoxifen, 4-OH-tamoxifen, and raloxifen). These results suggest that in PSMCs, 17␤E inhibits chemotactic and mitogenic effects of platelet-derived growth factor-BB as well as p38 and p42/44 MAPK phosphorylation. In contrast, 17␤E promotes in PAECs the phosphorylation of p42/44 and p38 MAPK as well as the migration and proliferation of these cells. Key Words: 17␤-estradiol Ⅲ smooth muscle Ⅲ endothelium Ⅲ mitogen-activated protein kinase R estenosis, occurring in 20% to 40% of patients, is currently the primary limitation of percutaneous transluminal coronary angioplasty. 1 Estrogens play an important role in bone maintenance, in the cardiovascular system, and in the growth, differentiation, and biological activity of various tissues. 2 Moreover, numerous in vivo studies in various animal models have demonstrated that the neointimal formation induced after balloon injury is increased in the absence of estrogen but is decreased in its presence. 3 The protective effects of 17␤-estradiol (17␤E) are related to favorable changes in the plasma lipid profile, 4 to the inhibition of vascular smooth muscle cell (VSMC) proliferation 5 and migration, 6 to the relaxation of coronary vessels through endothelial NO synthase (eNOS) activity, 7 and to the reduction of platelet and monocyte aggregation, 8 tumor necrosis factor-␣ release, 9 and extracellular matrix synthesis. 10 We have shown that local delivery of 17␤E reduces the neointimal thickness produced by coronary balloon injury in a porcine model. 11 Estrogen can bind 2 estrogen receptors (ERs), ER␣ and ER␤, which are expressed in all vascular cell types. 12 The classic genomic mechanism, or long-term effect of estrogen on vascular tissues, is dependent on a change in gene expression. Most recently, a second mechanism related to the direct effect of estrogen has been identified. 13 Several studies have demonstrated that 17␤E can activate many intracellular signaling responses. 14 The mitogen-activated protein kinase (MAPK) cascade plays a central role in the cellular signal transdu...

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“…50 Delayed delivery failed to prevent neointima formation in rabbits. 51 WHI was a primary prevention trial conducted in "healthy" women. However, similar to HERS the participants were older (50 to 79 years), with only 10% of the participants between 50 and 54 years old and 20% between 54 and 59 years old.…”

Section: Potential Factors Responsible For the Divergent Outcomes Of mentioning

confidence: 99%

Hormone Replacement Therapy and Cardiovascular Disease

et al. 2004

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Abstract-Observational studies in humans and experimental studies in animals and isolated cells supported the widely held belief that hormone replacement therapy protects the cardiovascular system from disease. To nearly everyone's astonishment, the Women's Health Initiative Study and the Heart and Estrogen/Progestin Replacement Study overturned the conclusion that hormone replacement therapy protects the cardiovascular system and, in fact, supported the opposite view that such therapy may actually increase the risk of cardiovascular disease. Observational Studies Suggest HRT Has Beneficial Cardiovascular EffectsIn modern societies, cardiovascular disease is the main cause of morbidity and mortality in men and women. Women, however, are comparatively spared. For example, in people younger than age 65 years, the prevalence of coronary heart disease (CHD) is several-fold higher in men. 3,4 Although CHD prevalence increases with age in both genders, before the age of 65 years the relationship between age and CHD prevalence is shifted rightward by 5 years in women; 5,6 compared with postmenopausal women, CHD deaths are rare in premenopausal women. 7 Autopsy studies demonstrated increased CHD in oophorectomized young women, 8 and several studies demonstrated an increased risk of cardiovascular disease in women with bilateral oophorectomy without HRT compared with those receiving HRT. 9,10 Women with natural early-onset menopause who did not use HRT had a greater likelihood for CHD compared with age-matched premenopausal women. 9,11 Also, studies reported an inverse relationship between age at natural menopause and mortality from CHD 12,13 and carotid atherosclerosis. 14 Bush et al demonstrated that HRT was associated with reduced all-cause mortality in postmenopausal women, 15 primarily because of favorable effects on high-density lipoprotein. 16 Barrett-Connor and Bush 8 reported that many, but not all, cross-sectional and prospective studies demonstrated a statistically significant reduction in CHD in women taking HRT, and Grady et al 17 presented a meta-analysis of published observational studies and reported that HRT was associated with one-third less fatal CHD. An up-to-date meta-analysis of 25 observational studies conducted between 1976 and 1996 showed that the relative risk for CHD in women who ever used HRT compared with never users was 0.70. 18 The Nurses' Health Study was a comprehensive investigation conducted in 121 700 female nurses aged 30 to 55 years. In the latest report, compiled with data from 70 533 postmenopausal women followed-up for 20 years, the overall risk of CHD in current users of HRT was reduced, with a relative risk of 0.61 after adjustment for age and cardiovascular risk factors. 19

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17β-estradiol, gender independently, reduces atheroma development but not neointimal proliferation after balloon injury in the rabbit aorta

Cited by 13 publications

References 61 publications

Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen

Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen

Estrogen Regulation of Endothelial and Smooth Muscle Cell Migration and Proliferation

Hormone Replacement Therapy and Cardiovascular Disease

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