Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies

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.