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Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies
Xiaoyu Yu1,2, Cong Cui2, Jiyong He1
1Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
Background:
Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, with inflammation central to disease progression. Emerging evidence reveals intricate crosstalk between metabolic reprogramming and epigenetic modifications in cardiovascular inflammatory injury, offering novel therapeutic strategies.
Objective:
This review elucidates the regulatory mechanisms underlying the metabolic-epigenetic axis in cardiovascular inflammation and explores both conventional and traditional Chinese medicine (TCM)-based intervention strategies.
Results:
Three findings are highlighted: (i) the succinate-hypoxia-inducible factor 1α (HIF-1α)-interleukin-1β (IL-1β) and itaconate-nuclear factor erythroid 2-related factor 2 (Nrf2) axes form an opposing pair defining macrophage polarization; (ii) acetyl-CoA, α-ketoglutarate (α-KG), lactate, and β-hydroxybutyrate (β-OHB) couple metabolism to histone modifications (H3K27ac, H3K27me3, H3K18la, H3K9ac) and DNA 5-hydroxymethylcytosine (5hmC), establishing trained immunity; (iii) mitochondrial dysfunction (mtDNA-cGAS-STING; mitochondrial ROS-NLRP3 inflammasome) and ferroptosis (GPX4/ACSL4) integrate these signals at the organelle level. TCM compounds (berberine, Shengmai Injection, tanshinone IIA, ginsenosides) modulate this axis at multiple nodes, with clinical support from the Phase III China Tongxinluo Study in Acute Myocardial Infarction (CTS-AMI) trial.
Conclusions:
The metabolic-epigenetic axis offers a tractable framework for precision anti-inflammatory cardiovascular therapy. Mechanistic studies and biomarker-guided trials are required to validate combined TCM-based interventions.
Insights
Cardiovascular inflammation involves metabolic and epigenetic changes. Traditional Chinese medicine compounds show promise in targeting this metabolic-epigenetic axis for novel therapies.
Area of Science:
- Cardiovascular research
- Epigenetics
- Metabolic reprogramming
Background:
- Cardiovascular diseases (CVDs) are a leading cause of death globally.
- Inflammation is a key driver in CVD progression.
- Metabolic reprogramming and epigenetic modifications are increasingly recognized in cardiovascular inflammatory injury.
Purpose of the Study:
- To review the regulatory mechanisms of the metabolic-epigenetic axis in cardiovascular inflammation.
- To explore conventional and Traditional Chinese Medicine (TCM)-based intervention strategies.
Main Methods:
- Review of existing literature on metabolic and epigenetic crosstalk in cardiovascular inflammation.
- Analysis of key molecular pathways, including macrophage polarization, histone modifications, DNA methylation, and organelle-level signaling.
- Evaluation of TCM compounds and clinical trial data.
Main Results:
- The succinate-HIF-1α-IL-1β and itaconate-Nrf2 axes regulate macrophage polarization.
- Metabolites like acetyl-CoA and α-KG link metabolism to histone modifications and DNA 5hmC, establishing trained immunity.
- Mitochondrial dysfunction and ferroptosis integrate these signals, with TCM compounds modulating this axis.
Conclusions:
- The metabolic-epigenetic axis provides a framework for precision anti-inflammatory cardiovascular therapy.
- Further mechanistic studies and biomarker-guided trials are needed to validate TCM-based interventions.
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