Magnesium deficiency causes a reversible, metabolic, diastolic cardiomyopathy

Man Liu, Hong Liu, Feng Feng, An Xie, Gyeoung Jin Kang, Yang Zhao, Cody R. Hou, Xiaoxu Zhou, Samuel C. Dudley

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Dietary Mg intake is associated with a decreased risk of developing heart failure, whereas low circulating Mg level is associated with increased cardiovascular mortality. We investigated whether Mg deficiency alone could cause cardiomyopathy. METHODS AND RESULTS: C57BL/6J mice were fed with a low Mg (low-Mg, 15– 30 mg/kg Mg) or a normal Mg (nl-Mg, 600 mg/kg Mg) diet for 6 weeks. To test reversibility, half of the low-Mg mice were fed then with nl-Mg diet for another 6 weeks. Low-Mg diet significantly decreased mouse serum Mg (0.38±0.03 versus 1.14±0.03 mmol/L for nl-Mg; P<0.0001) with a reciprocal increase in serum Ca, K, and Na. Low-Mg mice exhibited impaired cardiac relaxation (ratio between mitral peak early filling velocity E and longitudinal tissue velocity of the mitral anterior annulus e, 21.1±1.1 versus 15.4±0.4 for nl-Mg; P=0.011). Cellular ATP was decreased significantly in low-Mg hearts. The changes were accompanied by mitochondrial dysfunction with mito-chondrial reactive oxygen species overproduction and membrane depolarization. cMyBPC (cardiac myosin-binding protein C) was S-glutathionylated in low-Mg mouse hearts. All these changes were normalized with Mg repletion. In vivo (2-(2,2,6,6-tetra methylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride treatment during low-Mg diet improved cardiac relaxation, increased ATP levels, and reduced S-glutathionylated cMyBPC. CONCLUSIONS: Mg deficiency caused a reversible diastolic cardiomyopathy associated with mitochondrial dysfunction and oxidative modification of cMyBPC. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure.

Original languageEnglish (US)
Article numbere020205
JournalJournal of the American Heart Association
Volume10
Issue number12
DOIs
StatePublished - 2021

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health R01 HL104025 (Dr Dudley) and R01 HL106592 (Dr Dudley).

Publisher Copyright:
© 2021 The Authors.

Keywords

  • Ca handling
  • Diastolic dysfunction
  • Hypomagnesemia
  • Mitochondrial dysfunction

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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