Estrogen modulation of left ventricular remodeling in the aged heart

Xu, Yi; Arenas, Ivan A.; Armstrong, Stephen J.; Davidge, Sandra T.

doi:10.1016/s0008-6363(02)00705-8

Cited by 107 publications

(95 citation statements)

References 36 publications

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“…21 Although uterus weight decreased with ovariectomy in young and in senescent SHRs, the loss of uterine mass was less pronounced in senescent SHRs, which supports the hypothesis that uterus mass in sham-operated aged rats is less representative for estrogen action.…”

Section: Discussionsupporting

confidence: 60%

“…Estrogen effects on cardiac hypertrophy in senescent rats are at present not fully understood. Xu et al 21 reported on increased left ventricular remodeling in ovariectomized adult SpragueDawley rats that was prevented by E2 substitution. However, the aim of these studies, which were conducted in normotensive rats, was clearly different from the present study and not designed to compare the efficiency of E2 substitution between young and adult rats.…”

Section: Discussionmentioning

confidence: 99%

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Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Jazbutyte

Kruchten

et al. 2006

Hypertension

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Abstract-Clinical trials failed to show a beneficial effect of postmenopausal hormone replacement therapy, whereas experimental studies in young animals reported a protective function of estrogen replacement in cardiovascular disease. Because these diverging results could in part be explained by aging effects, we compared the efficacy of estrogen substitution to modulate cardiac hypertrophy and cardiac gene expression among young (age 3 months) and senescent (age 24 months) spontaneously hypertensive rats (SHRs), which were sham operated or ovariectomized and injected with placebo or identical doses of 17␤-estradiol (E2; 2 g/kg body weight per day) for 6 weeks (nϭ10/group). Blood pressure was comparable among sham-operated senescent and young SHRs and not altered by ovariectomy or E2 treatment among young or among senescent rats. Estrogen substitution inhibited uterus atrophy and gain of body weight in young and senescent ovariectomized SHRs, but cardiac hypertrophy was attenuated only in young rats. Cardiac estrogen receptor-␣ expression was lower in intact and in ovariectomized senescent compared with young SHRs and increased with estradiol substitution in aged rats. Plasma estradiol and estrone levels were lower not only in sham-operated but surprisingly also in E2-substituted senescent SHRs and associated with a reduction of hepatic 17␤-hydroxysteroid dehydrogenase type 1 enzyme activity, which converts weak (ie, estrone) into potent estrogens, such as E2. Aging attenuates the antihypertrophic effect of estradiol in female SHRs and is associated with profound alterations in cardiac estrogen receptor-␣ expression and estradiol metabolism. These observations contribute to explain the lower efficiency of estrogen substitution in senescent SHRs. (Hypertension. 2006;48:579-586.)

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Jazbutyte

Kruchten

et al. 2006

Hypertension

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“…The influence of the dietary compounds may occur through estrogenic effects on endogenous sex steroid receptors. These receptors have been implicated in cardiac growth in other models (32,33). We investigated the possibility that diet contributes to the phenotype via a sex steroid receptor-mediated mechanism.…”

Section: Resultsmentioning

confidence: 99%

Soy Diet Worsens Heart Disease in Mice

Stauffer

Konhilas

Luczak

et al. 2006

Obstetrical & Gynecological Survey

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We report that dietary modification from a soy-based diet to a casein-based diet radically improves disease indicators and cardiac function in a transgenic mouse model of hypertrophic cardiomyopathy. On a soy diet, males with a mutation in the α-myosin heavy chain gene progress to dilation and heart failure. However, males fed a casein diet no longer deteriorate to severe, dilated cardiomyopathy. Remarkably, their LV size and contractile function are preserved. Further, this diet prevents a number of pathologic indicators in males, including fibrosis, induction of β-myosin heavy chain, inactivation of glycogen synthase kinase 3β (GSK3β), and caspase-3 activation.

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“…extracellular matrix remodeling; ovariectomy; gender; hypertrophy; hormone; collagen; MT1-MMP; ventricle THE RISKS AND BENEFITS ASSOCIATED with estrogen replacement therapy remain uncertain. Conflicting results regarding the effect of estrogen replacement on the outcome of cardiovascular disease have been obtained from population studies, animal models, and clinical trials (2,16,20,21,32,33,61). The inconsistency of these findings demonstrates the lack of understanding of the mechanisms by which estrogen exerts its beneficial effects on the cardiovascular system.…”

mentioning

confidence: 99%

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

Voloshenyuk

Gardner

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Our previous studies demonstrate that 17␤-estradiol limits chronic volume overload-induced hypertrophy and improves heart function in ovariectomized rats. One possible cardioprotective mechanism involves the interaction between estrogen, estrogen receptors, and proteins of the extracellular matrix (ECM). The impact of estrogen deficiency and replacement on left ventricular (LV) hypertrophy and ECM protein expression was studied using five female rat groups: intact sham-operated, ovariectomized sham-operated, intact with volume overload, ovariectomized with volume overload, and ovariectomized with volume overload treated with estrogen. After 8 wk, LV protein extracts were evaluated by Western blot analysis for matrix metalloproteinase-2 (MMP-2) and MMP-9, MT1-MMP, tissue inhibitors of MMPs (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4, collagens type I and III, and estrogen receptor ␣ and ␤ expression. MMP proteolytic activity was assessed by zymography. All volume-overloaded groups exhibited LV hypertrophy, which was associated with a loss of interstitial collagen and perivascular fibrosis. After 8 wk of volume overload, 70% of ovariectomized rats developed heart failure, in contrast to only one intact rat. A downregulation of MMP-2, estrogen receptor-␣ (ER␣), and ER␤, and upregulation of MMP-9 and MT1-MMP were found in the volume-overloaded hearts of ovariectomized rats. Estrogen treatment improved TIMP-2/MMP-2 and TIMP-1/MMP-9 protein balance, restored ER␣ expression, and prevented MMP-9 activation, perivascular collagen accumulation and development of heart failure. However, estrogen did not fully restore ER␤ expression and did not prevent the increase of MMP-9 expression or loss of interstitial collagen. These results support that estrogen limits undesirable ECM remodeling and LV dilation, in part, through modulation of ECM protein expression in volume-overloaded hearts of ovariectomized rats. extracellular matrix remodeling; ovariectomy; gender; hypertrophy; hormone; collagen; MT1-MMP; ventricle THE RISKS AND BENEFITS ASSOCIATED with estrogen replacement therapy remain uncertain. Conflicting results regarding the effect of estrogen replacement on the outcome of cardiovascular disease have been obtained from population studies, animal models, and clinical trials (2,16,20,21,32,33,61). The inconsistency of these findings demonstrates the lack of understanding of the mechanisms by which estrogen exerts its beneficial effects on the cardiovascular system. Using a rodent model, we demonstrated that hearts of intact female rats are resistant to chronic volume overload-induced adverse cardiac remodeling and dysfunction (12). This apparent cardioprotection is lost following ovariectomy (6). Estrogen replacement delays the development of left ventricular (LV) hypertrophy and dilation, and it prevents the onset of congestive heart failure (CHF) in ovariectomized rats with volume overload (13). However, the mechanisms of estrogen's protective effects in prevention of adverse myocardial remodeling remain unclear.Changes in extra...

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Estrogen modulation of left ventricular remodeling in the aged heart

Abstract: Removal of ovarian hormones increased LV remodeling in the aged rat, which could be attenuated by estrogen replacement. Moreover, regulation of Ang II receptor expression could be a mechanism by which estrogen may modulate heart remodeling.

Cited by 107 publications

References 36 publications

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Soy Diet Worsens Heart Disease in Mice

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

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