LncRNA MDRL Mitigates Atherosclerosis through miR-361/SQSTM1/NLRP3 Signaling

Area of Science:

• Molecular Biology
• Cardiovascular Biology
• RNA Biology

Background:

• Long non-coding RNAs (lncRNAs) are crucial in gene regulation and disease.
• NLRP3 inflammasome and vascular smooth muscle cell (VSMC) apoptosis contribute to atherosclerosis.
• Mitochondrial dynamic related lncRNA (MDRL) role in these processes is unclear.

Purpose of the Study:

• To investigate MDRL's role in modulating NLRP3 inflammasome activation and VSMC apoptosis.
• To determine MDRL's protective effects against atherosclerosis.
• To elucidate the underlying molecular mechanism involving miR-361 and SQSTM1.

Main Methods:

• In vivo studies using LDLR knockout mice on a high-fat diet.
• In vitro studies with mouse aortic smooth muscle cells.
• Techniques included TUNEL staining, qRT-PCR, Western blot, RIP, and luciferase reporter assays.

Main Results:

• MDRL was downregulated, while NLRP3 and miR-361 were upregulated in atherosclerotic plaques.
• MDRL overexpression attenuated plaque burden and stability by inhibiting NLRP3 inflammasome and VSMC apoptosis.
• MDRL suppressed miR-361, which directly targets SQSTM1, thereby inhibiting NLRP3 inflammasome activation.

Conclusions:

• MDRL alleviates NLRP3 inflammasome activation and VSMC apoptosis via the miR-361/SQSTM1/NLRP3 pathway in atherogenesis.
• MDRL and miR-361 inhibition are potential therapeutic targets for atherosclerosis.
• These findings offer novel insights into lncRNA-mediated regulation of vascular disease.