Wnt2 Contributes to the Development of Atherosclerosis

Area of Science:

• Cardiovascular Biology
• Cellular Signaling
• Molecular Medicine

Background:

• Atherosclerosis is a chronic inflammatory arterial disease with incompletely understood molecular mechanisms.
• Endothelial-to-mesenchymal transition (EndMT) is implicated in disease progression but requires detailed mechanistic elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms of TGF-β-induced EndMT in human aortic endothelial cells (HAECs).
• To identify key signaling pathways involved in TGF-β-mediated EndMT and their role in atherosclerosis.

Main Methods:

• Cultured HAECs were treated with TGF-β to induce EndMT.
• Short hairpin RNA (shRNA) screening was used to identify essential signaling components.
• Wnt signaling pathway involvement was assessed.
• LDLR-/- mice on a high-fat diet were analyzed for Wnt2 expression in atherosclerotic lesions.

Main Results:

• TGF-β induced EndMT in HAECs, characterized by mesenchymal marker expression (α-SMA, PDGFRα) and loss of endothelial markers (VE-cadherin, CD31).
• Wnt2 signaling was identified as essential for TGF-β-mediated EndMT in HAECs.
• Elevated Wnt2 protein levels were observed in atherosclerotic lesions of LDLR-/- mice.

Conclusions:

• TGF-β activates EndMT in HAECs via a Wnt2-dependent pathway.
• Wnt2 signaling plays a role in atherosclerosis development in vivo.
• Wnt2 represents a potential therapeutic target for atherosclerosis.