Inhibiting YAP1 reduced abdominal aortic aneurysm formation by suppressing adventitial fibroblast phenotype transformation and migration

Abstract

AbstractBACKGROUNDThe 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.METHODSElastase-induced and Cacl2-induced mice AAA model were used in this study, we applied YAP1 inhibitor-Verteporfinin vivoto explore the role of YAP1 in AAA information;in vitro, Verteporfin and YAP1-siRNA were used to intervened TGF-β1 induced fibroblasts phenotype transformation and migration model.RESULTSAt first, we use immunohistochemistry (IHC) and western blotting (WB) to compare the expression of YAP1 in aneurysm tissues of AAA patients with normal adjacent vascular tissues, we found that the expression of YAP1 in AAA tissues was significantly increased, and YAP1 mainly increased in adventitia. YAP1 also upregulated in elastase-induced and Cacl2-induced mice AAA model. Then, we diminished YAP1 function with YAP1 inhibitor-Verteporfin in above mice AAA model, AAA incident rate was remarkably declined, and the collagen deposition in the adventitia was alleviated obviously. Afterwards, we studied the effect of YAP1 on the function of AF, we found that the process of AF transforming to myofibroblast and migration were almost completely eliminated after inhibiting YAP1 expression.CONCLUSIONSThis 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.