MicroRNA Regulation in Vascular Smooth Muscle Cells

MicroRNAs constitute a pivotal regulatory layer governing the behaviour of vascular smooth muscle cells (VSMCs), orchestrating the balance between a quiescent, contractile state and a proliferative, synthetic phenotype. These small non-coding RNAs modulate gene expression networks by fine-tuning messenger RNA stability and translation. In VSMCs, microRNAs influence key processes including cell proliferation, migration, extracellular matrix remodelling and inflammatory signalling. Dysregulation of specific microRNAs contributes to pathological vascular remodelling manifesting as neointimal hyperplasia, atherosclerosis and restenosis. Emerging evidence reveals intricate crosstalk between microRNAs and other regulatory molecules such as long non-coding RNAs, RNA-binding proteins and alternative splicing machinery. Together, these layers of post-transcriptional control dictate VSMC phenotypic plasticity and represent attractive targets for therapeutic intervention to prevent or reverse vascular disease.

Research from Nature Portfolio

Recent studies have applied Oxford Nanopore long-read RNA sequencing to primary human aortic VSMCs treated with growth factors and microRNA mimics. This approach uncovered thousands of previously unannotated splice variants that diversify the VSMC transcriptome. Distinct patterns of exon usage were associated with phenotypic stimuli, indicating that alternative splicing collaborates with microRNA networks to fine-tune functional outcomes. A novel unannotated transcript of the CISD1 gene was validated and shown to modulate the contractile-synthetic switch, illustrating how full-length transcript analysis can reveal new regulatory players in VSMC biology.

MicroRNA Regulation in Vascular Smooth Muscle Cells publication trend

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

Technical terms

microRNA (miRNA): Small non-coding RNA molecules (~22 nucleotides) that post-transcriptionally regulate gene expression by binding target messenger RNAs.

Long non-coding RNA (lncRNA): RNA transcripts longer than 200 nucleotides that regulate gene expression through diverse mechanisms, including molecular sponging of proteins or RNAs.

Phenotypic switch: The process by which VSMCs transition between a contractile, quiescent state and a synthetic, proliferative state.

Neointimal hyperplasia: Thickening of the innermost layer of a blood vessel due to VSMC proliferation and migration, often leading to luminal narrowing.

Alternative splicing: Generation of multiple mRNA isoforms from a single gene via inclusion or exclusion of specific exons, increasing proteomic diversity.

References

1. Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia. Cardiovascular Research (2024).
2. Nanopore long-read RNA sequencing reveals functional alternative splicing variants in human vascular smooth muscle cells. Communications Biology (2023).
3. MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. International Journal of Biological Sciences (2019).