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September 17, 2021Biology of Sex DifferencesOpen Access

Cardio-specific Ampkα2 deletion in mice led to progressive left ventricular systolic dysfunction, cardiac fibrosis, and mitochondrial cardiolipin remodeling in males, but not in females.

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Why the study?

AMPK regulates cellular energetics and may exert non-metabolic effects, but its specific cardiac roles remain to be deciphered without peripheral organ confounding.

Population

Cardio-specific inducible Ampkα2 gene deletion mouse model

Comparison

Cardio-specific Ampkα2 deficiency vs controls in male and female mice, and ovariectomy in females

Design

Preclinical animal study

Key result

Cardio-specific Ampkα2 deletion in mice led to progressive left ventricular systolic dysfunction, cardiac fibrosis, and mitochondrial cardiolipin remodeling in males, but not in females.

Authors

LGLucile GrimbertMSMaría-Nieves SanzMGMélanie Gressette

Discussion

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Overview

May warrant sex-specific AMPK targeting in HF; leaves open human translation and sex-stratified trials.

Structured PICO

P
Population
Adult male and female mice with a cardio-specific inducible deletion of Ampkα2, evaluated 16 weeks after tamoxifen injection.
I
Intervention
Cardio-specific inducible gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2), with ovariectomy in a subset of females
O
Outcome
Left ventricular systolic dysfunction, cardiac fibrosis, and mitochondrial function (complex I-driven respiration, cardiolipin rearrangement)surrogate

Main Result

Absolute Event Rate: 71.1% vs 78.3%

p-value: p=<0.05

AMPK plays a sex-specific role in cardiac mitochondrial function and fibrosis, which may have clinical implications for using AMPK activators to treat heart failure.

Limitations

  • Animal model findings may not fully translate to human clinical heart failure.
  • The exact molecular mechanisms underlying the protective effects of female hormones against AMPK loss require further investigation.

Cite This Study

Grimbert et al. (2021) studied Cardiac dysfunction and fibrosis. Cardio-specific Ampkα2 deletion vs. Control mice (Ampkα2 f/f treated with tamoxifen) was evaluated on Left ventricular ejection fraction in males at 16 weeks (p=<0.05). Cardio-specific Ampkα2 deletion in mice led to progressive left ventricular systolic dysfunction, cardiac fibrosis, and mitochondrial cardiolipin remodeling in males, but not in females.

synapsesocial.com/papers/6a7bd3e07cc40aa1f8df8e0dhttps://doi.org/10.1186/s13293-021-00394-z
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1AMP-Activated Protein Kinase α2 Deficiency Affects Cardiac Cardiolipin Homeostasis and Mitochondrial Function2007 · 53 citations
  2. 2AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism2015 · 74 citations
  3. 35′-AMP Activated Protein Kinase is Involved in the Regulation of Myocardial β-Oxidative Capacity in Mice2012 · 17 citations
  4. 4Adverse Effects of AMP-Activated Protein Kinase α2-Subunit Deletion and High-Fat Diet on Heart Function and Ischemic Tolerance in Aged Female Mice2016 · 15 citations
  5. 5Role of the α<sub>2</sub>-isoform of AMP-activated protein kinase in the metabolic response of the heart to no-flow ischemia2006 · 92 citations