The Metabolic-Inflammatory Axis in Hypertrophic Cardiomyopathy

Q: What is the clinical evidence from this study?

Study design: Editorial. Population: Hypertrophic cardiomyopathy. Intervention: Pioglitazone and R-pioglitazone vs. Untreated control. Primary outcome: Left ventricular wall thickness and interstitial fibrosis.

Q: What does this research mean for the field?

The metabolic-inflammatory axis is a key pathophysiological component of hypertrophic cardiomyopathy, and targeting it with pioglitazone or R-pioglitazone attenuates structural remodeling and fibrosis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Katharina J. Ermer; Vasco Sequeira

doi:10.1016/j.jacbts.2026.101619

July 1, 2026JACC Basic to Translational ScienceOpen Access

The Metabolic-Inflammatory Axis in Hypertrophic Cardiomyopathy

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Graphical abstract published by JACC Basic to Translational Science — Graphical abstract · Published by JACC Basic to Translational Science · CC BY

Key Points

Determine whether targeting the metabolic-inflammatory axis with pioglitazone or its R-enantiomer can reverse pathological cardiac remodeling and inflammation in hypertrophic cardiomyopathy.
Administered pioglitazone (pio) and its R-enantiomer (R-pio) to α-MHC 719/+ hypertrophic cardiomyopathy mice receiving cyclosporine A to accelerate disease onset.
Evaluated myocardial remodeling and pathways using echocardiography, histology, proteomics, RNA sequencing, immunohistochemistry, and plasma cytokine profiling.
Both pio and R-pio reduced left ventricular wall thickness and interstitial fibrosis, with R-pio exhibiting a stronger antifibrotic reduction (>95% vs ∼65%).
Treatments restored mitochondrial pyruvate carrier 1 (MPC1) and respiratory chain proteins while dampening pro-fibrotic and pro-hypertrophic signaling pathways (Wnt, MAPK, SMAD).
Both compounds reduced myocardial macrophage accumulation (IBA1+ and CD68+ cells), and R-pio normalized the circulating inflammatory markers CCL17 and interleukin-10.

PICO

P

Population

Hypertrophic cardiomyopathy

I

Intervention / Comparator

Pioglitazone and R-pioglitazone vs Untreated control

O

Primary Outcome

Left ventricular wall thickness and interstitial fibrosis

Limitations

The mouse model requires cyclosporine A (a broad immunosuppressant) to accelerate disease onset.
Most mechanistic interpretations rest on transcript and protein signatures and lack functional validation.
Translation from a single sarcomeric mouse model leaves open whether the same mechanisms operate across other sarcomere-gene variants or in genotype-negative HCM.

Implication

Preclinical study demonstrates that pioglitazone and its R-enantiomer reverse remodeling and inflammation in hypertrophic cardiomyopathy mice, highlighting a metabolic therapeutic strategy.

Abstract

[Figure: see text]

Discussion

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Cite This Study

Ermer et al. (2026) conducted an editorial in Hypertrophic cardiomyopathy. Pioglitazone and R-pioglitazone vs. Untreated control was evaluated on Left ventricular wall thickness and interstitial fibrosis.

synapsesocial.com/papers/6a7475b8d93df8ecca090daa https://doi.org/10.1016/j.jacbts.2026.101619

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The Metabolic-Inflammatory Axis in Hypertrophic Cardiomyopathy

Figures

Key Points

PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

The Metabolic-Inflammatory Axis in Hypertrophic Cardiomyopathy

Figures

Key Points

PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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