Depressed calcium cycling contributes to lower ischemia tolerance in hearts of estrogen-deficient rats

Gábor Artúr Dunay, Péter Paragi, Levente Sára, N. Ács, Bernadett Balázs, Viktor Ágoston, Csaba Répás, Tamás Ivanics, Zsuzsanna Miklós

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: Estrogens enhance ischemia tolerance (IT) in the myocardium, the mechanism of which remains unclear. We investigated the effects of long-term estrogen deprivation on the intracellular calcium (Ca2+i) transient of the heart and its possible influence on IT. Methods: Hearts of ovariectomized (OVX) and sham-operated (control) adult female rats (some receiving estrogen therapy) were studied 10 weeks after surgical operation: control (n = 8), OVX (n = 10), sham-operated estrogen-substituted (n = 7), and ovariectomized estrogen-substituted (n = 9). In vivo heart function was assessed by echocardiography, whereas Ca2+i transients were recorded, concomitantly with left ventricular pressure and coronary flow, by Indo-1 surface fluorometry in isolated Langendorff-perfused hearts. Isolated hearts were subjected to a 30-minute global ischemia-30-minute reperfusion protocol. Left ventricular expression of myocardial sarcoendoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban (PLB), and Ser16-phosphorylated PLB was measured. Results: Ovariectomy did not influence resting cardiac function in vivo or ex vivo. However, Ca2+ removal was slower. During ischemia, Ca2+i elevation and ischemic contracture were more pronounced after ovariectomy. Postischemic restitution of inotropic function (developed pressure; +dP/dtmax) and lusitropic function (-dP/dtmax) and Ca2+i transient recovery (amplitude; ±dCa2+i/dtmax) were decreased in OVX hearts. Sarcoendoplasmic reticulum Ca2+-ATPase expression was unaltered, whereas PLB and Ser16-phosphorylated PLB levels were higher after ovariectomy. All effects of ovariectomy were restored by estrogen therapy. Conclusions: Ovariectomy impairs myocardial Ca2+ removal by increasing the expression of the SERCA2a inhibitor PLB. Defective Ca2+ transport causes ischemic Ca2+i overload and insufficient postischemic recovery of Ca2+i transients, which entail depressed hemodynamic restitution. Protection of intact Ca2+ cycling in the myocardium by estrogens plays a major role in enhancing IT.

Original languageEnglish
Pages (from-to)773-782
Number of pages10
JournalMenopause
Volume22
Issue number7
DOIs
Publication statusPublished - Jul 8 2015

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Estrogens
Ischemia
Ovariectomy
Calcium
Reticulum
Calcium-Transporting ATPases
Myocardium
Ischemic Contracture
Fluorometry
Ventricular Pressure
Reperfusion
Echocardiography
Hemodynamics
phospholamban
Pressure
Therapeutics

Keywords

  • Ca<sup>2+</sup><inf>i</inf> transients
  • Cardiac ischemia tolerance
  • Estrogen deficiency
  • Indo-1 fluorometry
  • Isolated heart
  • Sarcoendoplasmic reticulum Ca<sup>2+</sup>-ATPase

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Depressed calcium cycling contributes to lower ischemia tolerance in hearts of estrogen-deficient rats. / Dunay, Gábor Artúr; Paragi, Péter; Sára, Levente; Ács, N.; Balázs, Bernadett; Ágoston, Viktor; Répás, Csaba; Ivanics, Tamás; Miklós, Zsuzsanna.

In: Menopause, Vol. 22, No. 7, 08.07.2015, p. 773-782.

Research output: Contribution to journalArticle

Dunay, GA, Paragi, P, Sára, L, Ács, N, Balázs, B, Ágoston, V, Répás, C, Ivanics, T & Miklós, Z 2015, 'Depressed calcium cycling contributes to lower ischemia tolerance in hearts of estrogen-deficient rats', Menopause, vol. 22, no. 7, pp. 773-782. https://doi.org/10.1097/GME.0000000000000377
Dunay, Gábor Artúr ; Paragi, Péter ; Sára, Levente ; Ács, N. ; Balázs, Bernadett ; Ágoston, Viktor ; Répás, Csaba ; Ivanics, Tamás ; Miklós, Zsuzsanna. / Depressed calcium cycling contributes to lower ischemia tolerance in hearts of estrogen-deficient rats. In: Menopause. 2015 ; Vol. 22, No. 7. pp. 773-782.
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abstract = "Objective: Estrogens enhance ischemia tolerance (IT) in the myocardium, the mechanism of which remains unclear. We investigated the effects of long-term estrogen deprivation on the intracellular calcium (Ca2+i) transient of the heart and its possible influence on IT. Methods: Hearts of ovariectomized (OVX) and sham-operated (control) adult female rats (some receiving estrogen therapy) were studied 10 weeks after surgical operation: control (n = 8), OVX (n = 10), sham-operated estrogen-substituted (n = 7), and ovariectomized estrogen-substituted (n = 9). In vivo heart function was assessed by echocardiography, whereas Ca2+i transients were recorded, concomitantly with left ventricular pressure and coronary flow, by Indo-1 surface fluorometry in isolated Langendorff-perfused hearts. Isolated hearts were subjected to a 30-minute global ischemia-30-minute reperfusion protocol. Left ventricular expression of myocardial sarcoendoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban (PLB), and Ser16-phosphorylated PLB was measured. Results: Ovariectomy did not influence resting cardiac function in vivo or ex vivo. However, Ca2+ removal was slower. During ischemia, Ca2+i elevation and ischemic contracture were more pronounced after ovariectomy. Postischemic restitution of inotropic function (developed pressure; +dP/dtmax) and lusitropic function (-dP/dtmax) and Ca2+i transient recovery (amplitude; ±dCa2+i/dtmax) were decreased in OVX hearts. Sarcoendoplasmic reticulum Ca2+-ATPase expression was unaltered, whereas PLB and Ser16-phosphorylated PLB levels were higher after ovariectomy. All effects of ovariectomy were restored by estrogen therapy. Conclusions: Ovariectomy impairs myocardial Ca2+ removal by increasing the expression of the SERCA2a inhibitor PLB. Defective Ca2+ transport causes ischemic Ca2+i overload and insufficient postischemic recovery of Ca2+i transients, which entail depressed hemodynamic restitution. Protection of intact Ca2+ cycling in the myocardium by estrogens plays a major role in enhancing IT.",
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T1 - Depressed calcium cycling contributes to lower ischemia tolerance in hearts of estrogen-deficient rats

AU - Dunay, Gábor Artúr

AU - Paragi, Péter

AU - Sára, Levente

AU - Ács, N.

AU - Balázs, Bernadett

AU - Ágoston, Viktor

AU - Répás, Csaba

AU - Ivanics, Tamás

AU - Miklós, Zsuzsanna

PY - 2015/7/8

Y1 - 2015/7/8

N2 - Objective: Estrogens enhance ischemia tolerance (IT) in the myocardium, the mechanism of which remains unclear. We investigated the effects of long-term estrogen deprivation on the intracellular calcium (Ca2+i) transient of the heart and its possible influence on IT. Methods: Hearts of ovariectomized (OVX) and sham-operated (control) adult female rats (some receiving estrogen therapy) were studied 10 weeks after surgical operation: control (n = 8), OVX (n = 10), sham-operated estrogen-substituted (n = 7), and ovariectomized estrogen-substituted (n = 9). In vivo heart function was assessed by echocardiography, whereas Ca2+i transients were recorded, concomitantly with left ventricular pressure and coronary flow, by Indo-1 surface fluorometry in isolated Langendorff-perfused hearts. Isolated hearts were subjected to a 30-minute global ischemia-30-minute reperfusion protocol. Left ventricular expression of myocardial sarcoendoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban (PLB), and Ser16-phosphorylated PLB was measured. Results: Ovariectomy did not influence resting cardiac function in vivo or ex vivo. However, Ca2+ removal was slower. During ischemia, Ca2+i elevation and ischemic contracture were more pronounced after ovariectomy. Postischemic restitution of inotropic function (developed pressure; +dP/dtmax) and lusitropic function (-dP/dtmax) and Ca2+i transient recovery (amplitude; ±dCa2+i/dtmax) were decreased in OVX hearts. Sarcoendoplasmic reticulum Ca2+-ATPase expression was unaltered, whereas PLB and Ser16-phosphorylated PLB levels were higher after ovariectomy. All effects of ovariectomy were restored by estrogen therapy. Conclusions: Ovariectomy impairs myocardial Ca2+ removal by increasing the expression of the SERCA2a inhibitor PLB. Defective Ca2+ transport causes ischemic Ca2+i overload and insufficient postischemic recovery of Ca2+i transients, which entail depressed hemodynamic restitution. Protection of intact Ca2+ cycling in the myocardium by estrogens plays a major role in enhancing IT.

AB - Objective: Estrogens enhance ischemia tolerance (IT) in the myocardium, the mechanism of which remains unclear. We investigated the effects of long-term estrogen deprivation on the intracellular calcium (Ca2+i) transient of the heart and its possible influence on IT. Methods: Hearts of ovariectomized (OVX) and sham-operated (control) adult female rats (some receiving estrogen therapy) were studied 10 weeks after surgical operation: control (n = 8), OVX (n = 10), sham-operated estrogen-substituted (n = 7), and ovariectomized estrogen-substituted (n = 9). In vivo heart function was assessed by echocardiography, whereas Ca2+i transients were recorded, concomitantly with left ventricular pressure and coronary flow, by Indo-1 surface fluorometry in isolated Langendorff-perfused hearts. Isolated hearts were subjected to a 30-minute global ischemia-30-minute reperfusion protocol. Left ventricular expression of myocardial sarcoendoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban (PLB), and Ser16-phosphorylated PLB was measured. Results: Ovariectomy did not influence resting cardiac function in vivo or ex vivo. However, Ca2+ removal was slower. During ischemia, Ca2+i elevation and ischemic contracture were more pronounced after ovariectomy. Postischemic restitution of inotropic function (developed pressure; +dP/dtmax) and lusitropic function (-dP/dtmax) and Ca2+i transient recovery (amplitude; ±dCa2+i/dtmax) were decreased in OVX hearts. Sarcoendoplasmic reticulum Ca2+-ATPase expression was unaltered, whereas PLB and Ser16-phosphorylated PLB levels were higher after ovariectomy. All effects of ovariectomy were restored by estrogen therapy. Conclusions: Ovariectomy impairs myocardial Ca2+ removal by increasing the expression of the SERCA2a inhibitor PLB. Defective Ca2+ transport causes ischemic Ca2+i overload and insufficient postischemic recovery of Ca2+i transients, which entail depressed hemodynamic restitution. Protection of intact Ca2+ cycling in the myocardium by estrogens plays a major role in enhancing IT.

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KW - Cardiac ischemia tolerance

KW - Estrogen deficiency

KW - Indo-1 fluorometry

KW - Isolated heart

KW - Sarcoendoplasmic reticulum Ca<sup>2+</sup>-ATPase

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