LncRNA-RP11-714G18.1 suppresses vascular cell migration via directly targeting LRP2BP

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• RNA Biology

Background:

• Atherosclerotic cardiovascular disease is a major global health burden.
• Long noncoding RNAs (lncRNAs) are implicated in atherosclerosis pathogenesis.
• The specific roles and mechanisms of lncRNAs in vascular dysfunction remain unclear.

Purpose of the Study:

• To identify novel lncRNAs involved in atherosclerosis.
• To elucidate the functional role and molecular mechanism of RP11-714G18.1 in vascular dysfunction.
• To explore the therapeutic potential of targeting the identified lncRNA pathway.

Main Methods:

• Microarray analysis to identify differentially expressed lncRNAs in human atherosclerotic plaques.
• In vitro studies using human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) to assess RP11-714G18.1 function.
• Molecular assays including gene binding, expression analysis, and signaling pathway investigation.
• Correlation analysis of serum LRP2BP levels with clinical markers in atherosclerotic patients.

Main Results:

• RP11-714G18.1 expression was significantly reduced in human advanced atherosclerotic plaques.
• RP11-714G18.1 impaired VSMC and EC function, including reduced migration, EC-monocyte adhesion, and neoangiogenesis, while decreasing VSMC apoptosis and promoting nitric oxide production.
• RP11-714G18.1 directly binds and upregulates LRP2BP, which mediates the downregulation of MMP1, thereby inhibiting vascular cell migration.
• Serum LRP2BP levels correlated positively with HDL cholesterol and negatively with cardiac troponin I in patients.

Conclusions:

• RP11-714G18.1 exhibits athero-protective properties by mitigating vascular dysfunction.
• The RP11-714G18.1/LRP2BP/MMP1 signaling axis is a key mechanism underlying RP11-714G18.1's function.
• Targeting this pathway presents a potential therapeutic strategy for atherosclerosis.