Estrogen receptor alpha up‐regulation and redistribution in human heart failure

Mahmoodzadeh, Shokoufeh; Eder, Sarah; Nordmeyer, Johannes; Ehler, Elisabeth; Huber, Otmar; Martus, Peter; Weiske, Jörg; Pregla, Reinhard; Hetzer, Roland; Regitz‐Zagrosek, Vera

doi:10.1096/fj.05-5148com

Cited by 133 publications

(104 citation statements)

References 34 publications

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“…Levels of ER␤ mRNA, on the other hand, are higher in male than in female hearts. 57 The relevance of ER receptors to cardiac disease is implicated by the findings that both ER␣ and ER␤ are upregulated during human aortic stenosis. 58 Similarly, myocardium from patients with end-stage heart failure demonstrates elevated expression of ER␣ mRNA.…”

Section: Estrogen Receptors and The Heartmentioning

confidence: 99%

“…58 Similarly, myocardium from patients with end-stage heart failure demonstrates elevated expression of ER␣ mRNA. 57 The functional differences between the receptors are being elucidated with the help of mice that lack either ER␣ or ER␤. Both male and female mice that lack ER␣ are completely sterile because of immature uterine development and improper pituitary function.…”

Section: Estrogen Receptors and The Heartmentioning

confidence: 99%

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The Effects of Biological Sex and Diet on the Development of Heart Failure

Konhilas

Leinwand

2007

Circulation

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Section: Estrogen Receptors and The Heartmentioning

confidence: 99%

Section: Estrogen Receptors and The Heartmentioning

confidence: 99%

The Effects of Biological Sex and Diet on the Development of Heart Failure

Konhilas

Leinwand

2007

Circulation

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“…Clinical and animal studies showed the existence of sex differences in the development of myocardial hypertrophy and heart failure (HF). 22,[56][57][58] Women with HF have a better survival rate than men. In most models, death from HF occurs earlier in male than in female animals.…”

mentioning

confidence: 99%

Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men

Bukowska

Spiller²,

Wolke

et al. 2017

Exp Biol Med (Maywood)

171

183

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The present study demonstrates that estrogen affects the human atrial myocardium and mediates protective actions through estrogen receptors-(ER) dependent signaling. Estrogen substantially modulates the local RAS via downregulation of ACE and simultaneous upregulation of ACE2, AT2R and MAS expression levels. This is indicative of a shift of the classical RAS/ACE axis to the alternative, protective RAS/ACE2 axis. In support of this view, estrogen attenuated the expression of RAS-associated downstream effectors, LOX-1, and ICAM-1. A specific antagonist of ERa reversed the anti-inflammatory and anti-oxidative effects of estrogen in paced and nonpaced atrial tissue slices. In summary, our data demonstrate the existence of protective effects of estrogen in atrial tissue from elderly men which are at least in part, mediated by the regulation of local RAS homeostasis. AbstractData from animal experiments and clinical investigations suggest that components of the renin-angiotensin system are markedly affected by sex hormones. However, whether estrogen affects human atrial myocardium has not been investigated yet. In this study, we determined the effects of estrogen on key components of atrial renin-angiotensin system: angiotensin-converting enzyme, responsible for generation of angiotensin II and angiotensin-converting enzyme 2, counteracting majority of AngII effects, and different renin-angiotensin system receptors, AT1R, AT2R, and MAS. First, the expression levels of estrogen receptors mRNA were determined in right atrial appendages obtained from patients undergoing heart surgery. The amounts of estrogen receptor a and estrogen receptor b mRNA were similar between women (n ¼ 14) and men (n ¼ 10). Atrial tissue slices (350 mm) were prepared from male donors which were exposed to estrogen (1-100 nM; n ¼ 21) or stimulated at 4 Hz for 24 h in the presence or absence of 100 nM estrogen (n ¼ 16), respectively. The administration of estrogen did not change mRNA levels of estrogen receptors, but activated MAP kinases, Erk1/2. Furthermore, estrogen increased the amounts of angiotensin-converting enzyme 2-mRNA (1.89 AE 0.23; P < 0.05) but reduced that of angiotensin-converting enzyme-mRNA (0.78 AE 0.07, P < 0.05). In addition, the transcript levels of AT2R and MAS were upregulated by estrogen. Pacing of tissue slices significantly increased the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at both the mRNA and protein level. During pacing, administration of estrogen substantially lowered the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at the transcript (0.92 AE 0.21 vs. 2.12 AE 0.27 at 4 Hz) and protein level (0.94 AE 0.20 vs. 2.14 AE 0.3 at 4 Hz). Moreover, estrogen elicited anti-inflammatory and anti-oxidative effects on renin-angiotensin system-associated downstream effectors such as pro-oxidative LOX-1 and pro-inflammatory ICAM-1. An antagonist of estrogen receptor a reversed these anti-inflammatory and anti-oxidative effects of estrogen significantly. Overall, our results demo...

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“…This protection is linked to the beneficial effects of natural estrogen on lipid profile, insulin sensitivity and blood pressure. Nevertheless, the existence of a functional estrogen receptor in the ventricular myocardium suggests that estrogens could be double-edged knives which, beyond their protective effect, could affect the cellular physiology of cardiac tissues both genomically and nongenomically [15], leading to greater LVM. Obesity is a risk factor for LVH [16] [17].…”

Section: Discussionmentioning

confidence: 99%

Lifestyle Changes for Abdominal Obesity Prevention and Encouraging Fruit Consumption May Be Beneficial in Preventing Left Ventricular Hypertrophy in Sub-Saharan African and Maghreb

Annis¹,

Phanzu²,

Moussa³

et al. 2017

WJCD

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There is a growing body of evidence showing a close correlation between left ventricular mass with cardiovascular morbidity and overall mortality. Therefore, identifying the determinants of left ventricular hypertrophy can be of great importance for cardiovascular prevention, for prognosis and therapeutic intervention. Objective: To assess the prevalence and identify the independent determinants of echocardiographic left ventricular hypertrophy in The MAGhreb and Sub-Saharan Africa Left-Ventricul ArGEometry Study (MAG-SALVAGES) participants. Methods: The MAG-SALVAGES is a community based study in which 100 asymptomatic Black Sub-Saharan African (BSSA) and 189 white skin Maghreb within the age of 18 to 55 years underwent a resting echocardiography. Multivariate logistic regression analysis was utilized to identify the independent determinants of LVH left ventricular hypertrophy. Results: Men represented the majority of the enrolled participants: 173 (59.9%). Echocardiographic left ventricular hypertrophy was seen in 10 (3.5%) participants. Age ≥40 years, female gender, overall obesity, abdominal obesity, hypertension status and less fruit consumption were significantly associated with echocardiography left ventricular hypertrophy. After adjusting for confounding factors, age ≥40 years, female gender, abdominal obesity and less fruit consumption were independently and significantly associated with echocardiographic left ventricular hypertrophy, as illustrated in the following equation: Y = 0.36 + 0.162 age >40 years + 2.69 female gender + 2.52 abdominal How to cite this paper:

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Estrogen receptor alpha up‐regulation and redistribution in human heart failure

Cited by 133 publications

References 34 publications

The Effects of Biological Sex and Diet on the Development of Heart Failure

The Effects of Biological Sex and Diet on the Development of Heart Failure

Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men

Lifestyle Changes for Abdominal Obesity Prevention and Encouraging Fruit Consumption May Be Beneficial in Preventing Left Ventricular Hypertrophy in Sub-Saharan African and Maghreb

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