YAP1 up-regulation inhibits apoptosis of aortic dissection vascular smooth muscle cells

T. Liu, J. Xu, J.-L. Guo, C.-Y. Lin, W.-M. Luo, Y. Yuan, H. Liu, J. Zhang

Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Hubei, China. junzhangda@sina.com

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• Cardiology

OBJECTIVE: Elevated apoptosis of vascular smooth muscle cell (VSMC) is correlated with the occurrence of aortic dissection (AD). Yes-associated protein 1 (YAP1) is the major effector in Hippo-YAP signal pathway, which facilitates cell proliferation and suppressing apoptosis. Several studies have been performed regarding the relationship between YAP1 and AD pathogenesis. This study established the AD rat model to investigate possible roles of YAP1 in regulating VSMC apoptosis and AD pathogenesis.

MATERIALS AND METHODS: Cell apoptosis and YAP1 expression were compared between AD vascular tissues and normal rats. In vitro studies with rat thoracic VSMCs were divided into control, cyclic stretch, cyclic stretch + pIRES2-blank and cyclic stretch + pIRES2-YAP1 groups. Cell apoptosis rate, YAP1 and survivin expressions were measured. AD rats were divided into model, Ad-NC injection, and Ad-YAP1 injection group for the detection of AD formation rate, expressions of YPA1 and survivin, and VSMCs apoptosis.

RESULTS: Compared to control group, vascular cell apoptosis was increased, and YAP1 expression was reduced in AD rats. Cyclic stretch significantly induced VSMCs apoptosis. The over-expression of YAP1 up-regulated survivin and impeded the cell apoptosis induced by cyclic stretch. The treatment with Ad-YAP1 up-regulated the levels of YAP1 and survivin in AD model rat vascular tissues, and decreased apoptosis and AD formation rate/AD diameter/length.

CONCLUSIONS: YAP1 played a critical role in affecting VSMC apoptosis and AD pathogenesis. Up-regulation of YAP1 decreased VSMC apoptosis and AD formation.

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