How Do LncRNAs Talk to miRNAs? Decoding Their Dialogue in Atherosclerosis

Atherosclerosis, characterized by the formation of fibrofatty lesions in the arterial wall, remains a leading cause of global morbidity and mortality. Emerging evidence highlights the critical regulatory roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in atherogenesis. LncRNAs can function as competing endogenous RNAs (ceRNAs) by sponging miRNAs, thereby modulating the expression of downstream target mRNAs. This review summarizes current knowledge on lncRNA-miRNA-mRNA regulatory networks and their functional roles in the three major cell types involved in atherosclerotic plaque development: endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages. In ECs, these networks are implicated in inflammation, apoptosis, proliferation, angiogenesis, pyroptosis, and autophagy. In VSMCs, they regulate proliferation, apoptosis, and migration. In macrophages, they influence lipid metabolism, inflammatory responses, oxidative stress, and autophagy. Although the ceRNA mechanism is predominant, some lncRNAs also act as primary transcripts for miRNAs. Additionally, exosome-mediated non-coding RNA delivery mediates intercellular crosstalk, further expanding the complexity of RNA-based regulation in atherosclerosis. Despite significant progress, challenges remain due to the complexity and context-specificity of these networks. Further research is essential to elucidate these mechanisms and explore their potential as therapeutic targets for atherosclerosis.