Epigenetic Regulation in Hepatic and Cardiovascular Systems

Epigenetic regulation orchestrates gene expression programmes that underpin liver and cardiovascular homeostasis, integrating environmental cues such as cytokines, lipids and hypoxia. In the liver, dynamic modifications of chromatin—mediated by ATP-dependent remodellers, histone-modifying enzymes and DNA methylation machinery—govern the activation of hepatic stellate cells and endothelial-to-mesenchymal transition, central events in fibrosis. Parallel mechanisms in the cardiovascular system regulate smooth muscle phenotypic switching, inflammatory responses and lipid metabolism, with direct implications for atherosclerosis and cardiac remodelling. Recent advances have illuminated how key chromatin regulators, including SWI/SNF complexes, histone methyltransferases and deacetylases, establish cell-type-specific transcriptional landscapes. Unravelling these pathways reveals novel therapeutic targets to reverse maladaptive gene networks in chronic liver disease and cardiovascular pathology, underscoring the global significance of epigenetic interventions.

Research from Nature Portfolio

A seminal investigation demonstrated that myocardin-related transcription factor A (MKL1) orchestrates H3K4 trimethylation at NF-κB target promoters by recruiting the SET1 methyltransferase, thereby establishing a chromatin landscape primed for pro-inflammatory gene activation. Although performed in macrophages, this work provides a mechanistic template for understanding how chromatin remodelling couples transcription factor co-activators to histone modification machinery in both hepatic inflammation and vascular dysfunction. The study highlights a molecular bridge between epigenetic alteration and inflammatory signalling, processes integral to tissue injury and fibrotic remodelling in liver and cardiovascular disease.

Epigenetic Regulation in Hepatic and Cardiovascular Systems publication trend

The graph below shows the total number of articles in epigenetic regulation in hepatic and cardiovascular systems across all publications each year (not limited to Nature Index journals).

Technical terms

Chromatin remodelling: ATP-dependent alteration of nucleosome positioning to regulate DNA accessibility.

H3K4 trimethylation: A histone H3 lysine-4 methylation mark associated with transcriptional activation.

Hepatic stellate cells (HSCs): Liver pericytes that, upon activation, trans-differentiate into myofibroblasts driving fibrosis.

Myofibroblasts: Contractile, fibrogenic cells that deposit extracellular matrix in tissue injury.

Endothelial-to-mesenchymal transition (EndMT): Process by which endothelial cells acquire mesenchymal and fibrogenic phenotypes.

SREBP2: Sterol regulatory element-binding protein 2, a transcription factor controlling genes of cholesterol biosynthesis.

References

1. MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response. Scientific Reports (2017).
2. The chromatin remodeling protein BRG1 regulates HSC-myofibroblast differentiation and liver fibrosis. Cell Death & Disease (2023).
3. Targetable Brg1‐CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking. EMBO Molecular Medicine (2023).
4. Brahma Related Gene 1 (Brg1) Regulates Cellular Cholesterol Synthesis by Acting as a Co-factor for SREBP2. Frontiers in Cell and Developmental Biology (2020).