LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling

Area of Science:

• Molecular Biology
• Cardiovascular Research
• RNA Biology

Background:

• Long noncoding RNAs (lncRNAs) are implicated in cellular processes within the vessel wall.
• Atherosclerosis involves complex inflammatory pathways in the vascular endothelium.
• Identifying novel regulators of vascular inflammation is crucial for understanding atherosclerosis.

Purpose of the Study:

• To identify and characterize novel lncRNAs involved in vascular inflammation and atherosclerosis.
• To investigate the role of the identified lncRNA, VINAS, in atherosclerotic lesion development.
• To explore the molecular mechanisms by which VINAS regulates vascular inflammation.

Main Methods:

• RNA-Seq profiling of aortic intimal lesions to identify differentially expressed lncRNAs.
• In vivo studies using LDLR-/- mice to assess the effect of VINAS knockdown on atherosclerosis.
• In vitro loss- and gain-of-function studies in endothelial cells, smooth muscle cells, and macrophages to elucidate VINAS's regulatory mechanisms.
• Analysis of inflammatory markers, signaling pathways (NF-κB, MAPK), and leukocyte adhesion molecules.

Main Results:

• A novel lncRNA, VINAS, was identified and found to be enriched in the aortic intima.
• VINAS expression decreased with atherosclerotic progression and increased with regression.
• VINAS knockdown significantly reduced atherosclerotic lesion formation (55%) by suppressing vascular inflammation, independent of lipid levels.
• VINAS modulates NF-κB and MAPK signaling, decreasing key inflammatory markers and leukocyte adhesion molecules.
• The human ortholog DEPDC4 demonstrated similar anti-inflammatory effects in human endothelial cells.

Conclusions:

• VINAS is a critical regulator of vascular inflammation and plays a significant role in atherosclerosis.
• VINAS functions by modulating key inflammatory signaling pathways and adhesion molecule expression.
• VINAS and its human ortholog DEPDC4 represent potential therapeutic targets for vascular diseases.