Effect of ovariectomy on intracellular Ca<sup>2+</sup> regulation in guinea pig cardiomyocytes

Yang, Hsiang-Yu; Firth, John D.; Francis, Alice J.; Alvarez-Laviada, Anita; MacLeod, Kenneth T.

doi:10.1152/ajpheart.00249.2017

Cited by 18 publications

(36 citation statements)

References 70 publications

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“…However, an increase in Tau suggests impaired ‘active’ relaxation, likely related to alterations in calcium handling, which has been reported in other studies (Yang et al . ). The loss in stroke volume (and consequently in CO) in OVX does indicate that oestrogen depletion can contribute to impaired pump function.…”

Section: Discussionmentioning

confidence: 97%

Unmasking of oestrogen‐dependent changes in left ventricular structure and function in aged female rats: a potential model for pre‐heart failure with preserved ejection fraction

Bustamante

Garate‐Carrillo

Ito

et al. 2019

The Journal of Physiology

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Key points Heart failure with preserved ejection fraction (HFpEF) is seen more frequently in older women; risk factors include age, hypertension and excess weight. No female animal models of early stage remodelling (pre‐HFpEF) have examined the effects that the convergence of such factors have on cardiac structure and function. In this study, we demonstrate that ageing can lead to the development of mild chamber remodelling, diffuse fibrosis and loss of diastolic function. The loss of oestrogens further aggravates such changes by leading to a notable drop in cardiac output (while preserving normal ejection fraction) in the presence of diffuse fibrosis that is more predominant in endocardium and is accompanied by papillary fibrosis. Excess weight did not markedly aggravate such findings. This animal model recapitulates many of the features recognized in older, female HFpEF patients and thus, may serve to examine the effects of candidate therapeutic agents. Abstract Two‐thirds of patients with heart failure with preserved ejection fraction (HFpEF) are older women, and risk factors include hypertension and excess weight/obesity. Pathophysiological factors that drive early disease development (before heart failure ensues) remain obscure and female animal models are lacking. The study evaluated the intersecting roles of ageing, oestrogen depletion and excess weight on altering cardiac structure/function. Female, 18‐month‐old, Fischer F344 rats were divided into an aged group, aged + ovariectomy (OVX) and aged + ovariectomy + 10% fructose (OVF) in drinking water (n = 8–16/group) to induce weight gain. Left ventricular (LV) structure/function was monitored by echocardiography. At 22 months of age, animals were anaesthetized and catheter‐based haemodynamics evaluated, followed by histological measures of chamber morphometry and collagen density. All aged animals developed hypertension. OVF animals increased body weight. Echocardiography only detected mild chamber remodelling with ageing while intraventricular pressure–volume loop analysis showed significant (P < 0.05) decreases vs. ageing in stroke volume (13% OVX and 15% for OVF), stroke work (34% and 52%) and cardiac output (29% and 27%), and increases in relaxation time (10% OVX) with preserved ejection fraction. Histology indicated papillary and interstitial fibrosis with ageing, which was higher in the endocardium of OVX and OVF groups. With ageing, ovariectomy leads to the loss of diastolic and global LV function while preserving ejection fraction. This model recapitulates many cardiovascular features present in HFpEF patients and may help understand the roles that ageing and oestrogen depletion play in early (pre‐HFpEF) disease development.

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Section: Discussionmentioning

confidence: 97%

Unmasking of oestrogen‐dependent changes in left ventricular structure and function in aged female rats: a potential model for pre‐heart failure with preserved ejection fraction

Bustamante

Garate‐Carrillo

Ito

et al. 2019

The Journal of Physiology

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“…Four experimental groups were generated: sham-operated control, transaortic constriction (AC), transaortic constriction with ovariectomy (ACOV), and transaortic constriction with ovariectomy supplemented with 17β-estradiol (ACOV+E). Animals initially underwent ovariectomy (OV) through a bilateral flank approach, in which both ovaries were surgically removed ( 8 ). A minimum of 7 days between the OV and AC procedures allowed appropriate recovery.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that the long-term absence of ovarian hormones in the guinea pig leads to detrimental changes to intracellular Ca 2+ regulation in the heart, resulting in the formation of a proarrhythmic substrate ( 8 ). Studies on mice support the idea of Ca 2+ dysregulation following ovariectomy ( 9 , 10 ), and, in rats, it has been shown that estrogen can reduce incidence of arrhythmia following episodes of ischemia reperfusion ( 11 ).…”

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confidence: 99%

The Effect of Estrogen on Intracellular Ca2+ and Na+ Regulation in Heart Failure

Firth

Yang

Francis

et al. 2020

JACC: Basic to Translational Science

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“…Interestingly, supplementation with either E 2 or progesterone prevents the OVX-related reductions in cardiac SERCA expression and activity and Thr17 PLB phosphorylation (77). However, Yang et al (92) reported that cardiomyocytes from OVX guinea pigs have 22% larger SR Ca 2+ stores and higher frequency of Ca 2+ sparks and waves than sham animals; addition of E 2 prevents these changes. Similarly, Howlett's group showed that the caffeine-induced SR Ca 2+ release signal, an indirect indicator of SR Ca 2+ content, is larger in cardiomyocytes from OVX than from sham C57BL/6 mice (74).…”

Section: Estrogen Gper and Serca2a And Its Regulatory Proteinsmentioning

confidence: 99%

Female Heart Health: Is GPER the Missing Link?

et al. 2020

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The G Protein-Coupled Estrogen Receptor (GPER) is a novel membrane-bound receptor that mediates non-genomic actions of the primary female sex hormone 17β-estradiol. Studies over the past two decades have elucidated the beneficial actions of this receptor in a number of cardiometabolic diseases. This review will focus specifically on the cardiac actions of GPER, since this receptor is expressed in cardiomyocytes as well as other cells within the heart and most likely contributes to estrogen-induced cardioprotection. Studies outlining the impact of GPER on diastolic function, mitochondrial function, left ventricular stiffness, calcium dynamics, cardiac inflammation, and aortic distensibility are discussed. In addition, recent data using genetic mouse models with global or cardiomyocyte-specific GPER gene deletion are highlighted. Since estrogen loss due to menopause in combination with chronological aging contributes to unique aspects of cardiac dysfunction in women, this receptor may provide novel therapeutic effects. While clinical studies are still required to fully understand the potential for pharmacological targeting of this receptor in postmenopausal women, this review will summarize the evidence gathered thus far on its likely beneficial effects.

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Effect of ovariectomy on intracellular Ca²⁺ regulation in guinea pig cardiomyocytes

Abstract: 26This study addressed the hypothesis that long-term deficiency of ovarian hormones,

Cited by 18 publications

References 70 publications

Unmasking of oestrogen‐dependent changes in left ventricular structure and function in aged female rats: a potential model for pre‐heart failure with preserved ejection fraction

Unmasking of oestrogen‐dependent changes in left ventricular structure and function in aged female rats: a potential model for pre‐heart failure with preserved ejection fraction

The Effect of Estrogen on Intracellular Ca2+ and Na+ Regulation in Heart Failure

Female Heart Health: Is GPER the Missing Link?

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Effect of ovariectomy on intracellular Ca2+ regulation in guinea pig cardiomyocytes

Abstract: 26This study addressed the hypothesis that long-term deficiency of ovarian hormones,

Cited by 18 publications

References 70 publications

Unmasking of oestrogen‐dependent changes in left ventricular structure and function in aged female rats: a potential model for pre‐heart failure with preserved ejection fraction

Unmasking of oestrogen‐dependent changes in left ventricular structure and function in aged female rats: a potential model for pre‐heart failure with preserved ejection fraction

The Effect of Estrogen on Intracellular Ca2+ and Na+ Regulation in Heart Failure

Female Heart Health: Is GPER the Missing Link?

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Product

Resources

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Effect of ovariectomy on intracellular Ca²⁺ regulation in guinea pig cardiomyocytes