基于Yes相关蛋白/同源异型盒转录因子通路探讨淋巴管新生在高血压心肌重构中的作用  

Role of lymphatic vessel neogenesis in myocardial remodeling in hypertension based on YAP/PROX1 pathway

作　　者：刘晶晶 陈昌贵 孙茹雪 李立为 LIU Jingjing;CHEN Changgui;SUN Ruxue;LI Liwei(Cardiovascular Internal Medicine ICU,Wuhan NO.1 Hospital,Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,Wuhan 430022,China)

机构地区：[1]湖北省武汉市中西医结合医院(武汉市第一医院)心血管内科重症监护室,武汉430022

出　　处：《实用医学杂志》2023年第3期289-297,共9页The Journal of Practical Medicine

基　　金：湖北省卫生健康科研基金项目(编号:20210926)。

摘　　要：目的 基于Yes相关蛋白(YAP)/同源异型盒转录因子(PROX1)通路探讨淋巴管新生在高血压心肌重构中的作用。方法 将小鼠分为4组,每组10只:假手术(Sham)+YAP-KO组、TAC+YAP-KO组、Sham+WT组和TAC+WT组。通过超声心动图获得小鼠心动图参数。通过免疫组织化学染色分析小鼠心脏组织中淋巴管内皮细胞透明质酸受体1(LYVE1)表达。小鼠淋巴管内皮细胞(LECs)分为以下6组进行:对照(Control)组、AngⅡ+NC组、AngⅡ+si-YAP组、AngⅡ+YAP组、AngⅡ+si-YAP+Vector组和AngⅡ+si-YAP+PROX1组。通过伤口愈合试验和EDU染色检测LECs的迁移、增殖。结果 与TAC+WT组相比,TAC+YAP-KO组小鼠心脏质量比、心肌细胞大小和间质纤维化面积均显著增加(P <0.05),和淋巴微血管密度显著降低(P <0.05)。与对照组相比,AngⅡ+NC组愈合面积、细胞增殖、管形成数量显著下降(P <0.05),并且AngⅡ+si-YAP组下降程度较AngⅡ+NC组更大(P <0.05),而AngⅡ+YAP组的愈合面积、细胞增殖、管形成数量较AngⅡ+NC组显著增加(P <0.05)。与AngⅡ+si-YAP+Vector组相比,AngⅡ+si-YAP+PROX1组LECs的愈合面积、增殖细胞和管形成数量显著增加(P <0.05)。结论 YAP/PROX1信号通路介导的淋巴管新生可能是一种治疗压力过载引起的心脏功能障碍的潜在靶点。Objective To explore the role of lymphatic vessel neogenesis in myocardial remodeling in hypertension based on the Yes-associated protein(YAP)/homologous heterotypic cassette transcription factor(PROX1)pathway.Methods The mice were divided into Sham+YAP-KO group,TAC+YAP-KO group,Sham+WT group and TAC+WT group,with 410 mice in each group.Cardiac parameters were obtained by echocardiography.The expression of lymphatic vascular endothelial cell hyaluronan receptor 1(LYVE1)in mouse heart tissues was analyzed by immunohistochemical staining.Mouse lymphatic vessel endothelial cells(LECs)were divided into the following six groups:control group,AngⅡ+NC group,AngⅡ+si-YAP group,AngⅡ+YAP group,AngⅡ+si-YAP+Vector group and AngⅡ+si-YAP+PROX1 group.The migration and proliferation of LECs were detected by wound healing test and EDU staining.Results Compared with those in the TAC+WT group,the heart mass ratio,cardiomyocyte size and interstitial fibrosis area were significantly increased(P<0.05)and lymphatic microvessel density was significantly decreased(P<0.05)in the TAC+YAP-KO group.Compared with those in the control group,the healing area,cell proliferation,and number of tube formation were significantly decreased in the AngⅡ+NC group(P<0.05),and the decrease was more significantly in the AngⅡ+si-YAP group than in the AngⅡ+NC group(P<0.05),whereas the healing area,cell proliferation,and number of tube formation were significantly increased in the AngⅡ+YAP group when compared with the AngⅡ+NC group(P<0.05).The healing area,proliferating cells,and number of tube formation were significantly(P<0.05)increased in the LECs of the AngⅡ+si-YAP+PROX1 group when compared with the AngⅡ+si-YAP+Vector group.Conclusion The lymphangiogenesis mediated by YAP/PROX1 signaling pathway may be a potential target for the treatment of cardiac dysfunction caused by pressure overload.

关 键 词：Yes相关蛋白 同源异型盒转录因子 淋巴管新生 高血压 心肌重构 

分 类 号：R544.1[医药卫生—心血管疾病]