MicroRNA Regulation in Atherosclerosis Pathophysiology

Atherosclerosis arises from chronic inflammation, lipid accumulation and vascular remodelling within arterial walls. MicroRNAs (miRNAs) are short non-coding RNAs that fine-tune gene expression, orchestrating multiple processes in plaque initiation, progression and complication. Reduced or elevated levels of specific miRNAs in endothelial cells, vascular smooth muscle cells and macrophages impact endothelial integrity, apoptotic susceptibility, foam cell formation and inflammatory signalling. Dysregulated miRNAs contribute to maladaptive vascular remodelling by shifting smooth muscle cells from a contractile to a synthetic phenotype, promoting extracellular matrix deposition and neointima formation. Circulating miRNAs enclosed in exosomes reflect underlying pathology, offering emerging utility as minimally invasive diagnostic biomarkers. Therapeutic strategies to restore or inhibit selected miRNAs hold promise for stabilising plaques, attenuating vascular inflammation and improving patient outcomes on a global scale.

Research from Nature Portfolio

Longitudinal profiling of circulating miRNAs in a swine model of familial hypercholesterolaemia has identified temporal changes in plasma miRNAs correlating with early coronary lesion development. Specific miRNAs such as miR-138 and miR-152 exhibited high discriminatory power at preclinical stages, whereas miR-486 and miR-126-3p were prominent at more advanced time points, underscoring their potential as early detection biomarkers. A mechanistic study has demonstrated that endothelial Dicer deficiency reduces unstable miRNA expression, notably miR-103, and consequently enhances KLF4-dependent gene programmes that oppose endothelial activation. By disrupting the miR-103–KLF4 interaction, researchers achieved decreased monocyte adhesion and reduced lesion formation in hyperlipidaemic mice. Seminal work on miR-26a revealed its protective role against endothelial apoptosis through direct targeting of TRPC6, implicating cytosolic calcium signalling and mitochondrial pathways in lesion initiation and suggesting therapeutic potential for miRNA-based interventions.

MicroRNA Regulation in Atherosclerosis Pathophysiology publication trend

The graph below shows the total number of articles in microrna regulation in atherosclerosis pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): small non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to target messenger RNAs.

Endothelial apoptosis: programmed cell death of endothelial cells lining blood vessels, a critical event in plaque initiation.

Foam cell: lipid-laden macrophage or smooth muscle cell that contributes to atherosclerotic plaque formation.

Dicer: an endoribonuclease enzyme essential for the maturation of microRNAs.

Exosomes: extracellular vesicles that transport microRNAs and proteins between cells, influencing intercellular communication.

References

1. MicroRNAs as Potential Biomarkers in Atherosclerosis. International Journal of Molecular Sciences (2019).
2. Longitudinal dynamics of circulating miRNAs in a swine model of familial hypercholesterolemia during early atherosclerosis. Scientific Reports (2023).
3. Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4. Nature Communications (2016).
4. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis. Scientific Reports (2015).
5. Role of miR‐15a‐5p and miR‐199a‐3p in the inflammatory pathway regulated by NF‐κB in experimental and human atherosclerosis. Clinical and Translational Medicine (2023).
6. Blood-based circulating microRNAs as diagnostic biomarkers for subclinical carotid atherosclerosis: A systematic review and meta-analysis with bioinformatics analysis. Diabetes & Metabolic Syndrome Clinical Research & Reviews (2023).