Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Hubei, China.
Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4632-4639.
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.
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.
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.
YAP1 played a critical role in affecting VSMC apoptosis and AD pathogenesis. Up-regulation of YAP1 decreased VSMC apoptosis and AD formation.
血管平滑肌细胞（VSMC）凋亡增加与主动脉夹层（AD）的发生有关。Yes 相关蛋白 1（YAP1）是 Hippo-YAP 信号通路的主要效应因子，促进细胞增殖，抑制细胞凋亡。已有多项研究探讨了 YAP1 与 AD 发病机制的关系。本研究建立 AD 大鼠模型，探讨 YAP1 调节 VSMC 凋亡及 AD 发病机制的可能作用。
比较 AD 血管组织与正常大鼠的细胞凋亡和 YAP1 表达。将大鼠胸主动脉平滑肌细胞分为对照组、循环拉伸组、循环拉伸+pIRES2-空白组和循环拉伸+pIRES2-YAP1 组，分别检测细胞凋亡率、YAP1 和 survivin 的表达。AD 大鼠分为模型组、Ad-NC 注射组和 Ad-YAP1 注射组，检测 AD 形成率、YPA1 和 survivin 的表达及 VSMCs 凋亡。
与对照组相比，AD 大鼠血管细胞凋亡增加，YAP1 表达减少。循环拉伸明显诱导 VSMCs 凋亡。YAP1 的过表达上调 survivin，抑制循环拉伸诱导的细胞凋亡。Ad-YAP1 治疗可上调 AD 模型大鼠血管组织中 YAP1 和 survivin 的水平，降低细胞凋亡和 AD 形成率/AD 直径/AD 长度。
YAP1 在影响 VSMC 凋亡和 AD 发病机制中起关键作用。YAP1 的上调可减少 VSMC 凋亡和 AD 形成。
