MicroRNA-939 governs vascular integrity and angiogenesis through targeting γ-catenin in endothelial cells

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Angiogenesis Research

Background:

• Coronary collateral circulation (CCC) acts as a natural bypass, improving outcomes in coronary artery disease (CAD).
• MicroRNAs (miRNAs) are key regulators of physiological and pathological processes, including angiogenesis essential for CCC.
• The specific role of microRNA-939 (miR-939) in angiogenesis and CCC remains largely uncharacterized.

Purpose of the Study:

• To investigate the expression of miR-939 in CAD patients.
• To elucidate the function of miR-939 in angiogenesis.
• To identify potential targets of miR-939 involved in vascular regulation.

Main Methods:

• Analysis of circulating miR-939 expression in CAD patients with varying CCC sufficiency.
• In vitro studies using human umbilical vein endothelial cells (HUVECs) to assess the effects of miR-939 modulation on cell proliferation, adhesion, migration, and tube formation.
• Identification of miR-939 targets using molecular techniques, including assessment of translational repression.

Main Results:

• Circulating miR-939 levels were significantly down-regulated in CAD patients with sufficient CCC compared to those with poor CCC.
• Overexpression of miR-939 in HUVECs inhibited proliferation, adhesion, and tube formation, while promoting migration.
• Knockdown of miR-939 produced opposite effects on HUVEC functions.
• Gamma-catenin (γ-catenin) was identified as a direct target of miR-939, mediating its effects on angiogenesis.

Conclusions:

• Circulating miR-939 is downregulated in CAD patients with robust coronary collateral circulation.
• MiR-939 negatively regulates angiogenesis and vascular integrity by directly targeting γ-catenin.
• MiR-939 represents a potential biomarker for assessing CCC and a therapeutic target for CAD management.