Estrogen supplement prevents the calcium hypersensitivity of cardiac myofilaments in ovariectomized rats

doi:10.1016/S0024-3205(99)00623-2

Life Sciences

Volume 66, Issue 6, 2000, Pages 533-543

https://doi.org/10.1016/S0024-3205(99)00623-2 Get rights and content

Summary

Our previous biochemical and mechanical studies have demonstrated an increase in Ca⁺ s sensitivity of cardiac myofilaments in ovariectomized rats. To test whether the body weight gain associated with ovariectomy contributed some effects to the changes in myofibrillar functions, the relations of pCa (-log Ca⁺ m molar concentration) to actomyosin adenosine triphosphatase (ATPase) activity of isolated myofibrillar preparations from 10-week pair-fed ovariectomized rats were compared with those from sham-operated controls. Despite similar body weights, the maximum myofibrillar ATPase activity was significantly lower in pair-fed ovariectomized rats as compared to that of sham-operated controls. In addition, the pCa-actomyosin ATPase relationship of pair-fed ovariectomized hearts still demonstrated a significant leftward shift in pCa₀ ( (− log half-maximally Ca⁺ a activation) from that of sham-operated controls. To find out which hormone was responsible for the observed increase in myofibrillar Ca⁺ s sensitivity, different sex hormone supplemental regimens were administered to ovariectomized rats. Subcutaneous injection of estrogen (5 μg/rat) or estrogen plus progesterone (1 mg/rat) three times a week could effectively prevent the changes in body weight, heart weight, and uterine weight of the ovariectomized animals. Moreover, supplements of either estrogen or progesterone could prevent a decrease in maximum ATPase activity. In contrast, only the estrogen replacement could abolish the Ca⁺ h hypersensitivity of the myofilaments in these ovariectomized rats. These results suggest differential cardio-regulatory effects of ovarian sex hormones on the Ca⁺ a activation of the myofilaments.

References (38)

J. Wattanapermpool
Life Sciences
(1998)
F.D. Kolodgie et al.
J. Mol. Cell. Cardiol.
(1997)
S.G. Carter et al.
J. Biochem. Biophys. Methods
(1982)
J.F.Y. Hoh et al.
J. Mol. Cell. Cardiol.
(1978)
S. Schiaffino et al.
Trends Cardiovasc. Med.
(1993)
K.A. Palmiter et al.
J. Biol. Chem.
(1996)
J. Wattanapermpool et al.
Am. J. Physiol.
(1999)
R.J. Solaro et al.
Circulation
(1993)
R.J. Solaro
Heart Failure
(1994)
S. Heyder et al.
Pflugers Arch.
(1995)

M.R. Wolff et al.

Circ. Res.

(1995)

M.R. Wolff et al.

J. Clin. Invest.

(1996)

J. Scheuer et al.

Circ. Res.

(1987)

E.D. Pagani et al.

Am. J. Physiol.

(1983)

O.H. Lowry et al.

J. Biol. Chem.

(1951)

U.K. Laemmli

Nature

(1970)

A. Fabiato

J. Gen. Physiol.

(1981)

J.A. Lee et al.

A. Malhotra et al.

Am. J. Physiol.

(1990)

Cited by (45)

Differing effects of estrogen deficiency on the contractile function of atrial and ventricular myocardium
2021, Biochemical and Biophysical Research Communications
Estrogen deficiency has a significant influence on the excitation-contraction coupling in the ventricular myocardium but its impact on the atrial contractile function has not been studied. We have compared the effects of estrogen deficiency on the contractility and cytosolic Ca²⁺ transient of single cardiomyocytes isolated from the left atrium (LA) and the left ventricle (LV) of rats subjected to ovariectomy (OVX) or sham surgery (Sham). The characteristics of actin-myosin interaction were studied in an in vitro motility assay. We found that OVX decreased the contractility of LV single cardiomyocytes but increased that of LA myocytes. The disturbance of ventricular mechanical function may be explained by the acceleration of Ca²⁺ transient and reduced Ca²⁺ sensitivity of the actin-myosin interaction. The augmentation of LA contractility may be explained by accelerated cross-bridge kinetics and increased end-diastolic sarcomere length, which may lead to elevated tension in atrial cells due to the Frank-Starling mechanism.
Sex specific mechanisms of myocardial hypertrophy and heart failure
2019, Sex Differences in Cardiovascular Physiology and Pathophysiology
Heart failure (HF) is one of the major health threats of western societies. Women are more likely to survive than men and HF in women frequently occurs at an older age and with less ischemic etiology than men. In western populations, HFpEF has a greater prevalence in women and HFrEF in men. Risk factors for HF differ in women and men. Hypertension contributes to the risk for heart failure in women to a greater extent than in men and diabetes is a stronger risk factor for HF in women than in men. The interaction between diabetes and atherogenic and prohypertrophic mechanisms and cardiovascular risk in women has been related to sexual hormones. Acute coronary syndromes (ACS) occur 3–4 times more often in men than women below age 60, but after 75 years women represent the majority of patients. IHD seems to lead more frequently to HF in women than in men. Dilated cardiomyopathy and hypertrophic cardiomyopathy are more frequent causes of HF in men than in women.
Endurance training restores spatially distinct cardiac mitochondrial function and myocardial contractility in ovariectomized rats
2019, Free Radical Biology and Medicine
Citation Excerpt :
Along these lines, it is well established in the literature that estrogen plays a significant role in cardiac excitation-contraction coupling by regulating sarcoplasmic reticulum (SR) function, myofilament calcium sensitivity and oxidative stress. On the other hand, estrogen deficiency leads to myocardial contractile dysfunction at least in part due to angiotensin II type 1 receptor activation [4–6]. Left ventricular dysfunction is accompanied by derangements in myocardial fuel metabolism and bioenergetics that contribute to the development and progression of the disease.
We previously demonstrated that the loss of female hormones induces cardiac and mitochondrial dysfunction in the female heart. Here, we show the impact of endurance training for twelve weeks, a nonpharmacological therapy against cardiovascular disease caused by ovariectomy and its contribution to cardiac contractility, mitochondrial quality control, bioenergetics and oxidative damage. We found that ovariectomy induced cardiac hypertrophy and dysfunction by decreasing SERCA2 and increasing phospholamban protein expression. Endurance training restored myocardial contractility, SERCA2 levels, increased calcium transient in ovariectomized rats but did not change phospholamban protein expression or cardiac hypertrophy. Additionally, ovariectomy decreased the amount of intermyofibrillar mitochondria and induced mitochondrial fragmentation that were accompanied by decreased levels of mitofusin 1, PGC-1α, NRF-1, total AMPK-α and mitochondrial Tfam. Endurance training prevented all these features except for mitofusin 1. Ovariectomy reduced O₂ consumption, elevated O₂^.- release and increased Ca²⁺-induced mitochondrial permeability transition pore opening in both mitochondrial subpopulations. Ovariectomy also increased NOX-4 protein expression in the heart, reduced mitochondrial Mn-SOD, catalase protein expression and increased protein carbonylation in both mitochondrial subpopulations, which were prevented by endurance training. Taken together, our findings show that endurance training prevented cardiac contractile dysfunction and mitochondrial quality control in ovariectomized rats.
Comprehensive assessment of sex hormones in Takotsubo syndrome
2018, International Journal of Cardiology
The detailed pathomechanism of Takotsubo syndrome (TS) is still elusive. Due to the predominance of postmenopausal females, a potential role of sex hormones has been suggested. However, the limited available data are contradictory. The aim of this study was to comprehensively assess the role of sex hormone levels in a large cohort of TS patients.
Serum samples of 57 female TS patients and 57 female patients with myocardial infarction (MI), matched for age (± 2 years) and repolarization disturbances were analyzed for estradiol (E2), estrone (E1), testosterone and androstenedione using liquid chromatography-tandem mass spectrometry.
There was no difference concerning the concentrations of E1 [pmol/l (IQR): 89.1 (62.5, 132.0) vs. 98.8 (63.3, 156.0), p = 0,441], testosterone [nmol/l (IQR): 0.67 (0.46, 1.00) vs. 0.80 (0.49, 1.08), p = 0.382] and androstenedione [nmol/l (IQR): 2.03 (1.57, 3.11) vs. 2.98 (1.48, 5.27), p = 0.244] between female TS and MI patients. Regarding E2, the majority of patients demonstrated concentrations below the detection limit of 30 pmol/l (TS: n = 41/54, 75.9%; MI: n = 32/53, 60.4%; p = 0.078). The remaining individuals with detectable E2 concentrations did not show a significant difference between TS and MI patients [pmol/l (IQR): 40.5 (33.0, 53.3) vs. 54.1 (37.9, 60.9); p = 0.20].
Altered sex hormone levels, especially an estradiol deficiency, could not be identified as a risk factor for TS.
Sex and Gender Specific Aspects-From Cells to Cardiovascular Disease
2017, Principles of Gender-Specific Medicine: Gender in the Genomic Era: Third Edition
Most cardiovascular diseases (CVD) differ in women and men in their epidemiology, manifestation, pathophysiology, treatment, and outcome. We discuss biological mechanisms of sex differences (SD) in CVD starting from their underlying reasons. We discuss SD in genetic mechanisms, epigenetic mechanisms, and sex hormones, as reviewed recently. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. We discuss resulting SD in cell function and animal models for adaptation of the CV system to internal and external stress, such as genetic variation, exercise, ischemia, pressure overload, hormonal disturbances, inflammation, over- and undernutrition, and pregnancy. We give an overview on SD in clinical syndromes, in ischemic disease, valvular heart disease, arrhythmia, cardiomyopathy, heart failure, and hypertension and here we include the effect of gender—differences between women and men, arising from attitudes toward disease and access to health care. Finally we make suggestions for future research directions.
Significant role of estrogen in maintaining cardiac mitochondrial functions
2015, Journal of Steroid Biochemistry and Molecular Biology
Citation Excerpt :
Previously, we demonstrated that many cellular and molecular changes in cardiac contraction and relaxation after a 10-week deprivation of ovarian sex hormones were similar to those observed in the heart disease condition. Supplementation with estrogen or progesterone after an ovariectomy yielded different protective results [25]. In this study, we further demonstrate that both estrogen and progesterone have regulatory roles in modulating mitochondrial structure and function, but exhibit some differences.
Increased susceptibility to stress-induced myocardial damage is a significant concern in addition to decreased cardiac performance in postmenopausal females. To determine the potential mechanisms underlying myocardial vulnerability after deprivation of female sex hormones, cardiac mitochondrial function is determined in 10-week ovariectomized rats (OVX). Significant mitochondrial swelling in the heart of OVX rats is observed. This structural alteration can be prevented with either estrogen or progesterone supplementation. Using an isolated mitochondrial preparation, a decrease in ATP synthesis by complex I activation in an OVX rat is completely restored by estrogen, but not progesterone. At basal activation, reactive oxygen species (ROS) production from the mitochondria is not affected by the ovariectomy. However, after incubated in the presence of either high Ca²⁺ or antimycin-A, there is a significantly higher mitochondrial ROS production in the OVX sample compared to the control. This increased stress-induced ROS production is not observed in the preparation isolated from the hearts of OVX rats with estrogen or progesterone supplementation. However, deprivation of female sex hormones has no effect on the protein expression of electron transport chain complexes, mitofusin 2, or superoxide dismutase 2. Taken together, these findings suggest that female sex hormones, estrogen and progesterone, play significant regulatory roles in maintaining normal mitochondrial properties by stabilizing the structural assembly of mitochondria as well as attenuating mitochondrial ROS production. Estrogen, but not progesterone, also plays an important role in modulating mitochondrial ATP synthesis.

View all citing articles on Scopus

View full text

Estrogen supplement prevents the calcium hypersensitivity of cardiac myofilaments in ovariectomized rats

Summary

Life Sciences

J. Mol. Cell. Cardiol.

J. Biochem. Biophys. Methods

J. Mol. Cell. Cardiol.

Trends Cardiovasc. Med.

J. Biol. Chem.

Am. J. Physiol.

Circulation

Heart Failure

Pflugers Arch.

Circ. Res.

J. Clin. Invest.

Circ. Res.

Am. J. Physiol.

J. Biol. Chem.

Nature

J. Gen. Physiol.

Am. J. Physiol.