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PMID-37961903 – Pan-ERR Agonists Ameliorate Heart Failure

PMID-37961903 – Pan-ERR Agonists Ameliorate Heart Failure

Teng S, Kim SH, Burris TP. Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circ Res. 2024;134(2):208-222.

Quick Reference

Property Value
PMID 37961903
DOI 10.1161/CIRCRESAHA.123.323624
Year 2024
Journal Circulation Research
Study Type Animal in vivo
Evidence Level V
Sample Mouse models of heart failure
Peptide(s) Studied SLU-PP-332

Key Findings

  • Pan-ERR agonists (SLU-PP-332 and related compounds) improved cardiac function in heart failure mouse models
  • Enhanced cardiac fatty acid oxidation capacity — restoring the heart's preferred fuel source
  • Improved mitochondrial function and biogenesis in cardiomyocytes
  • Reduced cardiac hypertrophy and fibrosis markers
  • ERRgamma activation was particularly important for cardiac-specific effects
  • Demonstrated that ERR agonism has therapeutic potential beyond skeletal muscle effects
  • Published in high-impact journal (Circulation Research) — elevates the scientific credibility of the ERR agonist class

Study Design

Preclinical study using mouse models of pressure-overload heart failure (transverse aortic constriction). Animals treated with pan-ERR agonists and assessed for cardiac function (echocardiography), mitochondrial parameters, and tissue analysis.

Limitations

  • Animal study only
  • Heart failure models may not fully recapitulate human disease
  • Same research group (Burris lab) as the metabolic syndrome studies
  • Cardiac doses/exposure levels not easily translatable to human dosing
  • IP administration route

Clinical Relevance

Expands the therapeutic potential of ERR agonists beyond obesity and exercise mimicry into cardiovascular medicine. The failing heart shifts from fatty acid oxidation to glucose metabolism — ERR agonists may restore the metabolic flexibility needed for optimal cardiac function. This is the first demonstration of cardiovascular benefits for this compound class, published in a top-tier cardiology journal.

Related

#research #animal-in-vivo #SLU-PP-332 #evidence-level-V