What question did this study set out to answer?

The research aims to investigate the harmful effects of methylmalonate on myocardial vulnerability and its potential as a therapeutic target.

January 10, 2026BMC Medicine0 citationsOpen Access

Methylmalonate accumulation contributes to myocardial vulnerability post-reperfusion: a novel therapeutic target and prognostic biomarker

SWShanjie WangHarbin Medical University JGJ. GuoOutcomes Research Consortium ZWZeng WangHebei Medical University

Key Result

Methylmalonate (MMA) accumulation worsens myocardial vulnerability post-reperfusion, suggesting that targeting MMA metabolism could reduce myocardial injury in AMI patients.

Key Points

The research aims to investigate the harmful effects of methylmalonate on myocardial vulnerability and its potential as a therapeutic target.
Analysis of MMA effects on myocardial tissue post-reperfusion
Comparison with succinate isomer impacts
Assessment of MMA as a prognostic biomarker in acute myocardial infarction
MMA accumulation increases myocardial vulnerability after reperfusion.
Targeting MMA metabolism may reduce myocardial injury.
MMA serves as a potential new biomarker for risk stratification in patients.

Structured PICO

Does targeting MMA metabolism via MMUT gene delivery reduce myocardial ischemia/reperfusion injury and incident heart failure in post-reperfusion AMI?

Population

Human cohorts: 11,410 adults from NHANES 1999-2004 (Cohort 1); 362 AMI survivors (Cohort 2); 1,353 STEMI survivors (Cohort 3). Animal models: C57BL/6 mice (Mmut-conditional knockout) and 12 Bama miniature pigs subjected to myocardial ischemia/reperfusion (I/R) injury.

Intervention

Cardiac Mmut-conditional knockout, exogenous MMA administration (DiMMA 25 mg/kg/day), and AAV9-containing MMUT gene delivery (1.26*10^13 in pigs).

Comparator

Wild-type littermates, sham operation, AAV9-GFP empty vector, or vehicle/succinate.

Outcome

Incident heart failure within 1-year follow-up (humans); infarct size, mitochondrial dysfunction, and cardiac remodeling post-I/R (animals).

Targeting mitochondrial MMA metabolism represents a promising therapeutic strategy for restoring mitochondrial quality and mitigating myocardial injury in patients with AMI and reperfusion.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

This study revealed an unrecognized harmful effect of MMA on myocardial vulnerability distinct from its isomer succinate. Targeting MMA metabolism represents a promising strategy to optimize risk stratification and mitigate myocardial injury in patients with AMI.

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