Abstract:

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 4 10 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 Ang Ⅱ+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 Ang Ⅱ+si⁃YAP+PROX1 group when compared with the AngⅡ+si⁃YAP+Vector group. Conclusion The lymphangio⁃ genesis mediated by YAP/PROX1 signaling pathway may be a potential target for the treatment of cardiac dysfunc⁃tion caused by pressure overload.

Key words:

Yes ? related protein, homozygous isoform cassette transcription factor, lymphovascular neogenesis, hypertension, myocardial remodeling