External stent ameliorates vein graft remodeling through Ajuba-mediated suppression of Hippo signaling pathway
Yi Yang1, Bei Qian1, Dingjie Zhou1
1Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
Abstract:
Saphenous vein grafts (SVGs), commonly used in coronary artery bypass graft procedures, are prone to failure due to intimal hyperplasia. Although the external stents have been applied to reduce mechanical stress and ameliorated vein graft remodeling, the biological mechanisms linked to mechanical stress remains incomplete. In this study, we identify biological significance of Ajuba, a LIM-domain protein, and defined its mechanism for stress-regulation of Hippo signaling pathway in SVGs. The in vivo application of external stents decreases the mechanical stress, downregulates Ajuba and maintains Hippo signaling pathway. Additionally, we developed an in vitro model to examine how mechanical stress influences Ajuba expression and its impact on the regulation of the Hippo signaling pathway, stimulating cell proliferation, invasion and cell cycle progression. Overall, our research unveils the mechanisms behind external stents and highlights Ajuba as a promising therapeutic target for preventing SVG failure.


