MicroRNA Regulation of Lipid Metabolism and Cardiovascular Health

MicroRNAs are small non-coding RNAs that fine-tune gene expression by targeting messenger RNAs for degradation or translational repression. In lipid metabolism they orchestrate biosynthesis, uptake, storage and efflux of cholesterol and fatty acids, thus influencing systemic homeostasis. Dysregulation of specific microRNAs contributes to the development of dyslipidaemia, nonalcoholic fatty liver disease, atherosclerosis and other cardiometabolic conditions. By modulating key nodes such as sterol regulatory element-binding proteins, ATP-binding cassette transporters and apolipoprotein assembly, microRNAs hold both mechanistic and therapeutic significance. Beyond intracellular control, circulating microRNAs emerge as minimally invasive biomarkers of cardiovascular risk. Integration of multi-omic data and preclinical models has highlighted the global relevance of microRNA-mediated networks, paving the way for precision interventions that restore lipid balance and protect vascular health.

Research from Nature Portfolio

Recent investigations have identified circulatory microRNAs with diagnostic potential in coronary artery disease. A pilot study in a South Asian cohort revealed that serum levels of miR-128-3p are significantly reduced in patients with angiographically confirmed disease, implicating this microRNA in cholesterol efflux pathways and foam-cell formation. Foundational work has demonstrated that miR-33, encoded within an intron of the SREBP2 gene, directly targets SREBP1 and other enzymes of lipid handling. Genetic deletion of miR-33 in mice led to exacerbation of diet-induced obesity and hepatic steatosis, underscoring its critical role in balancing lipid synthesis and export. In parallel, therapeutic inhibition of miR-29 in murine liver produced a striking 40% decrease in plasma cholesterol and reduced hepatic fatty acid content by attenuating lipogenic programmes. Transcriptomic analysis implicated upregulation of anti-lipogenic factors such as sirtuin 1 and aryl hydrocarbon receptor, illustrating the pleiotropic impact of microRNA modulation on metabolic gene networks.

MicroRNA Regulation of Lipid Metabolism and Cardiovascular Health publication trend

The graph below shows the total number of articles in microrna regulation of lipid metabolism and cardiovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): small non-coding RNA that post-transcriptionally modulates gene expression.

Cholesterol efflux: active removal of cholesterol from cells to extracellular acceptors.

SREBP: sterol regulatory element-binding protein, transcription factor governing lipid biosynthesis.

Apolipoprotein B (apoB): core protein essential for the formation and secretion of low-density lipoproteins.

Foam cell: lipid-laden macrophage that contributes to plaque development in atherosclerosis.

References

1. Effects of miR-33 Deficiency on Metabolic and Cardiovascular Diseases: Implications for Therapeutic Intervention. International Journal of Molecular Sciences (2023).
2. Role of miR-128-3p and miR-195-5p as biomarkers of coronary artery disease in Indians: a pilot study. Scientific Reports (2024).
3. MicroRNA-615-3p decreases apo B expression in human liver cells. Journal of Lipid Research (2024).
4. MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice. Nature Communications (2013).
5. Long‐term therapeutic silencing of miR‐33 increases circulating triglyceride levels and hepatic lipid accumulation in mice. EMBO Molecular Medicine (2014).
6. Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver. Scientific Reports (2015).