Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/β-catenin...

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• RNA Biology

Background:

• Atherosclerosis, a primary cause of stroke and heart disease, involves complex endothelial cell (EC) dysfunction.
• Endothelial cell proliferation and migration are critical in the initiation and progression of atherosclerotic lesions.
• The precise molecular mechanisms regulating EC behavior in atherosclerosis remain incompletely understood.

Purpose of the Study:

• To investigate the role of the long noncoding RNA HOTTIP in the pathogenesis of coronary artery disease (CAD).
• To determine the effect of HOTTIP on endothelial cell proliferation and migration.
• To elucidate the molecular pathway through which HOTTIP influences endothelial cell function.

Main Methods:

• Quantitative analysis of HOTTIP expression in human coronary artery disease tissues versus normal tissues.
• In vitro studies involving endothelial cells treated with TNF-α or PDGF-BB to induce proliferation.
• Manipulation of HOTTIP expression (overexpression and downregulation) in endothelial cells.
• Assessment of cell proliferation, migration, and expression of key proteins (cyclin D1, PCNA, β-catenin, c-Myc).
• Analysis of the Wnt/β-catenin signaling pathway activation.

Main Results:

• HOTTIP expression was significantly higher in CAD tissues compared to normal tissues.
• HOTTIP expression was upregulated in proliferating endothelial cells stimulated by TNF-α or PDGF-BB.
• Overexpression of HOTTIP enhanced endothelial cell proliferation and migration, increasing cyclin D1 and PCNA levels.
• Downregulation of HOTTIP suppressed endothelial cell proliferation and migration.
• HOTTIP overexpression induced β-catenin and c-Myc expression, indicating activation of the Wnt/β-catenin pathway.

Conclusions:

• Long noncoding RNA HOTTIP is upregulated in coronary artery disease and promotes endothelial cell proliferation and migration.
• HOTTIP exerts its pro-atherogenic effects by activating the Wnt/β-catenin signaling pathway.
• HOTTIP represents a potential therapeutic target for managing atherosclerosis and related cardiovascular diseases.