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Comprehensive plasma and tissue profiling reveals systemic metabolic alterations in cardiac hypertrophy and failure

Oliver J Müller1,2, Markus B Heckmann1,2, Lin Ding1,2

  • 1Internal Medicine III, University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg, Germany.

Cardiovascular Research
|November 13, 2018
PubMed
Abstract

Insights

Heart failure involves significant metabolic changes in the heart and body. Targeting carnitine transport via OCTN2 shows promise for treating heart failure.

Area of Science:

  • Cardiovascular Biology
  • Metabolomics
  • Molecular Cardiology

Background:

  • Heart failure is marked by structural and metabolic cardiac remodeling.
  • Understanding metabolic shifts during heart failure progression is crucial for therapeutic development.

Purpose of the Study:

  • To investigate complex metabolic alterations during the transition from pathological hypertrophy to heart failure.
  • To identify novel biomarkers and therapeutic targets from systemic metabolic profiling.

Main Methods:

  • Mice underwent transverse aortic constriction (TAC) or sham surgery.
  • Metabolomic and transcriptional profiling of plasma, liver, skeletal muscle, and heart tissues were performed at 2, 4, and 6 weeks post-surgery.
  • Cardiac overexpression of Organic Cation/Carnitine Transporter 2 (OCTN2) was investigated as a therapeutic strategy.

Main Results:

  • Progressive alterations in cardiac metabolic pathways and gene expression indicated impaired mitochondrial function and a metabolic switch.
  • Significant metabolic changes, including depletion of essential fatty acids, were observed in the liver and skeletal muscle.
  • Circulating metabolites, particularly fatty acids, correlated with cardiac defects and heart function decline.
  • Decreased carnitine shuttling preceded mitochondrial dysfunction, highlighting OCTN2's role.
  • Cardiac OCTN2 overexpression improved ejection fraction and reduced fibrosis in TAC mice.

Conclusions:

  • Systemic metabolic profiling reveals widespread alterations in heart failure.
  • Metabolic and transcriptional data identify novel biomarkers and potential therapeutic targets for heart failure.
  • Targeting carnitine transport through OCTN2 offers a promising therapeutic avenue for heart failure.
Keywords:
BiomarkersHeart failureMetabolismOCTN2Therapeutic target

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