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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
06:18

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause

Published on: August 13, 2019

Oestrogen confers cardioprotection by suppressing Ca2+/calmodulin-dependent protein kinase II

Y Ma1, W T Cheng, S Wu

  • 1Department of Physiology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

British Journal of Pharmacology
|May 9, 2009
PubMed
Abstract

Insights

Oestrogen protects the heart by suppressing Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). This mechanism is independent of beta-adrenoceptors and reduces cardiac apoptosis and damage during ischaemia/reperfusion.

Area of Science:

  • Cardiovascular physiology
  • Endocrinology
  • Molecular cardiology

Background:

  • Oestrogen (estrogen) provides cardioprotection, partly by down-regulating beta(1)-adrenoceptors and suppressing protein kinase A.
  • Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a signaling molecule activated by beta(1)-adrenoceptors that promotes apoptosis.

Purpose of the Study:

  • To investigate whether oestrogen protects the heart by suppressing CaMKII.
  • To determine the role of CaMKII in oestrogen-mediated cardioprotection during ischaemia/reperfusion.

Main Methods:

  • Assessed CaMKII expression and activity in rat hearts with and without ovariectomy and oestrogen replacement.
  • Examined the effects of CaMKII inhibition (KN93) and beta-adrenoceptor stimulation (isoprenaline) on cardiac function and apoptosis.
  • Quantified infarct size, lactate dehydrogenase release, and myocyte apoptosis.

Main Results:

  • Ovariectomy increased CaMKIIdelta and phosphorylated CaMKII, which was reversed by oestrogen.
  • Ovariectomized rats exhibited greater infarct size, LDH release, impaired contractility, and increased apoptosis upon ischaemia/reperfusion.
  • Oestrogen replacement and CaMKII blockade (KN93) both reversed the detrimental effects of ischaemia/reperfusion in ovariectomized rats.

Conclusions:

  • Oestrogen confers cardioprotection, at least partly by suppressing CaMKIIdelta.
  • This oestrogen effect on CaMKII is independent of beta-adrenoceptor signaling.
  • Targeting CaMKII represents a potential therapeutic strategy for oestrogen-deficient states.

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