Unraveling LncRNA GAS5 in Atherosclerosis: Mechanistic Insights and Clinical Translation.

Abstract

Atherosclerosis, a chronic inflammatory disease driving cardiovascular events, involves complex molecular networks where long non-coding RNAs (lncRNAs) are key regulators. This review synthesizes current knowledge on lncRNA Growth Arrest-Specific 5 (GAS5) in atherosclerosis, covering its expression, multifaceted roles in vascular cells, and molecular mechanisms. GAS5 is significantly upregulated in atherosclerotic plaques, exerting complex, cell-specific effects on vascular smooth muscle cells, macrophages, and endothelial cells. GAS5 modulates crucial pathophysiological processes like cell proliferation, apoptosis, inflammation, lipid metabolism, and foam cell formation, primarily by acting as a competing endogenous RNA (ceRNA) and through direct protein interactions. While promising as a biomarker, circulating GAS5 levels require further validation. Therapeutic strategies targeting GAS5, including antisense oligonucleotides (ASO) and small-molecule compounds, are under investigation. In conclusion, lncRNA GAS5 is a critical regulatory node in atherosclerosis pathobiology, offering significant opportunities for novel diagnostic and therapeutic interventions. Further research is vital to elucidate its intricate roles and translate these findings into clinical applications for atherosclerotic cardiovascular disease.