Department of General Intensive Care Unit, Key Laboratory of Early Warning and Intervention of Multiple Organ Failure, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Cell Mol Med. 2024 Nov;28(21):e70159. doi: 10.1111/jcmm.70159.
The adventitial fibroblast (AF) is the most abundant cell in the vascular adventitia, a few studies had confirmed that AF contributed to abdominal aortic aneurysm (AAA) development; YAP1 involved in several vascular diseases by promoting AF transformed to myofibroblast, the role of YAP1 in AAA is not clear yet. This study aims to determine whether YAP1 play a role in AAA process by regulating AF function. We found the expression of YAP1was significantly increased in aneurysm tissues of AAA patients compared to normal adjacent vascular tissues and mainly in adventitia. YAP1 also upregulated in elastase-induced and CaCl-induced mice AAA model. Suppressed YAP1 function with YAP1 inhibitor-Verteporfin declined AAA incident rate remarkably in mice, and the collagen deposition in the adventitia was alleviated obviously. Afterwards, we studied the effect of YAP1 on the function of AF, Verteporfin was used to block YAP1 in vitro, the process of AF transforming to myofibroblast and migration were almost completely eliminated after inhibiting YAP1 expression. This study demonstrated that YAP1 may play a key role in AAA development, inhibiting YAP1 significantly reduced AAA formation through suppressed the process of AF transformed to myofibroblast and migration.
血管外膜成纤维细胞（AF）是血管外膜中最丰富的细胞，有几项研究已经证实 AF 有助于腹主动脉瘤（AAA）的发展；YAP1 通过促进 AF 向肌成纤维细胞转化而参与多种血管疾病，YAP1 在 AAA 中的作用尚不清楚。本研究旨在通过调节 AF 功能来确定 YAP1 是否在 AAA 过程中发挥作用。我们发现与正常相邻血管组织相比，AAA 患者的血管外膜组织中 YAP1 的表达明显增加，主要在外膜中。弹性蛋白酶诱导和 CaCl2 诱导的小鼠 AAA 模型中 YAP1 的表达也上调。用 YAP1 抑制剂 Verteporfin 抑制 YAP1 功能可显著降低小鼠 AAA 的发生率，并明显减轻外膜中的胶原沉积。随后，我们研究了 YAP1 对 AF 功能的影响，用 Verteporfin 在体外阻断 YAP1，抑制 YAP1 表达后，AF 向肌成纤维细胞转化和迁移的过程几乎完全消除。本研究表明，YAP1 可能在 AAA 发展中起关键作用，抑制 YAP1 可通过抑制 AF 向肌成纤维细胞转化和迁移来显著减少 AAA 的形成。
