Low concentrations of 17β-estradiol protect single cardiac cells against metabolic stress-induced Ca2+ loading
Open accessAbstract
Objectives The main objective of the present study was to determine whether low physiological levels of estrogen directly protect cardiac cells against metabolic stress.Background The beneficial effect of estrogens on the cardiovascular system has been traditionally ascribed to decrease in peripheral vascular resistance and to an antiatherogenic action. Whether physiological concentrations of 17beta-estradiol (E2) are also able to protect cardiomyocytes against metabolic insult directly is unknown.Methods Isolated ventricular cardiomyocytes were loaded with the Ca2+-sensitive fluorescent dye Fluo-3 and imaged by a digital epifluorescence imaging system. In cardiac cells preincubated with hormones and/or drugs for 8 h, metabolic stress was induced by addition and removal of 2,4-dinitrophenol (DNP).Results In cardiomyocytes, a 3-min-long exposure to chemical hypoxia, followed by reoxygenation, produced intracellular Ca2+ loading independently of gender (female: 729 +/- 88 nmol/liter; male: 778 +/- 97 nmol/liter). Pretreatment with E2 (10 nmol/liter) significantly reduced the magnitude of hypoxia/reoxygenation-induced Ca2+ loading in female (E2-treated: 298 +/- 39 nmol/liter; untreated: 729 +/- 88 nmol/liter), but not in male (E2-treated: 1029 +/- 177 nmol/liter; untreated: 778 +/- 97 nmol/liter) cardiac cells. The protective action of E2 was not mimicked by the inactive estrogen stereoisomer, 10 nmol/liter 17alpha estradiol (17alpha estradiol-treated: 886 +/- 122 nmol/liter; untreated: 729 +/- 88 nmol/liter), and was abolished by tamoxifen (1 micromol/liter), which acts as an antagonist of E2 on estrogen receptors (E2 plus tamoxifen-treated: 702 +/- 98 nmol/liter; untreated: 729 +/- 88 nmol/liter).Conclusions In a gender-dependent manner, E2 directly protects cardiac cells against hypoxia-reoxygenation injury through an estrogen receptor-mediated mechanism. Such property of E2 may contribute to cardioprotection in the female gender.
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The bulk of studies evaluating sex differences in the AF-related risk of heart failure have showed no significant difference; however, a few studies have suggested higher risk in women.
“The bulk of studies evaluating sex differences in the AF-related risk of HF have showed no significant difference; however, a few studies have suggested higher risk in women (Supplementary Table S8).”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [102]
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- Authors
- Jovanović, S., Jovanović, A., Shen, W. K., & Terzic, A.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Jovanović, Aleksandar
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 36
- Issue
- 3
- Pages
- 948-952
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2035219321
- Cited by
- 65
- References
- 24
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2021: 3 · 2019: 5 · 2017: 1 · 2016: 3 · 2013: 1 · 2012: 6
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- University of Dundee
- Wellcome Trust (059528/Z/99/Z/JMW/CP/JF, 059528)
- British Heart Foundation
- Tenovus
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- estradiol, estrogen cardioprotection, cardiomyocytes, metabolic stress, hypoxia/reoxygenation injury, estrogen receptor, tamoxifen, 17α-estradiol, sex differences, 2,4-dinitrophenol, ischemia-reperfusion injury
- MeSH terms
- Animals, Hypoxia, Calcium, Estradiol, Estrogen Antagonists, Female, Guinea Pigs, Male, Myocardium, Osmolar Concentration, Oxygen, Sex Characteristics, Stress, Physiological, Tamoxifen
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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