MicroRNAs (miRNAs) have received most of the attention over the last decades in particular for their role in tempering gene expression. An increasing number of studies highlighting the importance of miRNAs in the development and progression of atherosclerosis have been performed. Recently, it was shown that miRNAs exert their role in the pathophysiology of atherosclerosis via the regulation of atherosclerosis-prone genes as well as their impact in regulating post-transcriptional gene expression. Hence, by affecting the level of synthesised protein within cells, they may be significant in driving the dysregulation that affects endothelial cells, smooth muscle cells and leukocytes, which initiates and augments the growth of an atherosclerotic plaque. Furthermore, the circulating levels of vascular cell-enriched miRNAs in patients could serve as a marker of disease severity and phenotypes. The accumulating evidence also indicates that their effects on atherosclerosis may allow us to exploit miRNAs as novel therapeutics or clinical biomarkers that may lead to better management of vascular diseases. Current reports providing insights into the impact of miRNAs and the mechanisms of their influences in atherosclerosis are reviewed here with a particular emphasis on studies that have been recently published in Arteriosclerosis, Thrombosis, and Vascular Biology.

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Objective: Perivascular adipose tissue (PVAT) plays a vital role in maintaining vascular homeostasis. However, most studies ascribed the function of PVAT in vascular remodeling to adipokines secreted by the perivascular adipocytes. Whether mesenchymal stem cells exist in PVAT and play a role in vascular regeneration remain unknown. Approach and Results: Single-cell RNA-sequencing allowed direct visualization of the heterogeneous PVAT-derived mesenchymal stem cells (PV-ADSCs) at a high resolution and revealed 2 distinct subpopulations, among which one featured signaling pathways crucial for smooth muscle differentiation. Pseudotime analysis of cultured PV-ADSCs unraveled their smooth muscle differentiation trajectory. Transplantation of cultured PV-ADSCs in mouse vein graft model suggested the contribution of PV-ADSCs to vascular remodeling through smooth muscle differentiation. Mechanistically, treatment with TGF-β1 (transforming growth factor β1) and transfection of microRNA (miR)-378a-3p mimics induced a similar metabolic reprogramming of PV-ADSCs, including upregulated mitochondrial potential and altered lipid levels, such as increased cholesterol and promoted smooth muscle differentiation. Conclusions: Single-cell RNA-sequencing allows direct visualization of PV-ADSC heterogeneity at a single-cell level and uncovers 2 subpopulations with distinct signature genes and signaling pathways. The function of PVAT in vascular regeneration is partly attributed to PV-ADSCs and their differentiation towards smooth muscle lineage. Mechanistic study presents miR-378a-3p which is a potent regulator of metabolic reprogramming as a potential therapeutic target for vascular regeneration.