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May 1, 2026

Ailanthone alleviates septic cardiomyopathy by attenuating MYST histone acetyltransferase 1 (MOF)-mediated H4K16 lactylation-driven inflammation.

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Why the study?

Elevated circulating lactate is a recognized prognostic biomarker in septic cardiomyopathy, but the mechanisms by which it exacerbates cardiac pathology are not fully understood.

Population

Cardiomyocytes in vitro and a murine model of sepsis

Comparison

Ailanthone treatment vs control in septic mice and in vitro cardiomyocytes

Design

Preclinical in vitro and in vivo animal study

Key result

Inhibition of hexokinase 2 with ailanthone attenuated myocardial injury and improved cardiac function in a murine model of sepsis by targeting the lactate-H4K16la pathway.

Authors

YZYi ZhouMMMeican MaCXChong Xu

Discussion

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Overview

Should not yet change septic cardiomyopathy practice; leaves open histone lactylation as hypothesis-generating therapeutic target.

Key Points

  • This study investigates the role of histone lactylation in linking metabolic dysregulation to cardiac dysfunction during sepsis.
  • In vitro assessment of lactate effects on LPS-induced inflammation in cardiomyocytes
  • Use of CUT&Tag to explore epigenetic mechanisms
  • Evaluation of ailanthone in a murine model of sepsis
  • Lactate increased inflammation and apoptosis in cardiomyocytes due to elevated H4K16 lactylation
  • H4K16 lactylation was linked to increased expression of inflammatory genes CXCL8 and CCL2
  • Ailanthone treatment in septic mice improved cardiac function and reduced myocardial injury

Structured PICO

P
Population
Cardiomyocytes in vitro and a murine model of sepsis
I
Intervention
Ailanthone (AIL), a specific hexokinase 2 (HK2) inhibitor
O
Outcome
Myocardial injury and cardiac functionsurrogate

Ailanthone attenuates myocardial injury and improves cardiac function in a murine model of septic cardiomyopathy by inhibiting HK2 and reducing MOF-mediated H4K16 lactylation-driven inflammation.

Cite This Study

Zhou et al. (2026) studied Septic cardiomyopathy. Ailanthone (AIL) was evaluated on Myocardial injury and cardiac function. Inhibition of hexokinase 2 with ailanthone attenuated myocardial injury and improved cardiac function in a murine model of sepsis by targeting the lactate-H4K16la pathway.

synapsesocial.com/papers/69f442fc967e944ac55666c2https://doi.org/10.1111/bph.70478
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