Open AccessYes‐associated protein mediates angiotensin II ‐induced vascular smooth muscle cell phenotypic modulation and hypertensive vascular remodelling
Author(s) -
Lin Maohuan,
Yuan Woliang,
Su Zizhuo,
Lin Caina,
Huang Tucheng,
Chen Yangxin,
Wang Jingfeng
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12517
Subject(s) - vascular smooth muscle , angiotensin ii , downregulation and upregulation , gene knockdown , microbiology and biotechnology , vascular remodelling in the embryo , gene silencing , endocrinology , medicine , losartan , receptor , biology , chemistry , cell culture , biochemistry , smooth muscle , gene , genetics
Abstract Objectives Yes‐associated protein ( YAP ) has been reported to regulate cell proliferation and differentiation. We aimed to characterize the role of YAP in angiotensin II (Ang II )‐induced hypertensive vascular remodelling ( HVR ) and vascular smooth muscle cells ( VSMC s) phenotypic modulation and to explore the underlying mechanisms. Materials and methods An HVR rat model was established by continuous Ang II infusion for 2 weeks. Western blotting, qRT ‐ PCR , and confocal microscopy were conducted to assess YAP expression. YAP ‐sh RNA interfering plasmid and adenovirus were constructed to knock down YAP . We used cell proliferation and migration assays, accompanied by pathway inhibitors, to evaluate the biological function and underlying mechanisms. Results Ang II upregulated YAP expression in the media of carotid artery; however, in vivo YAP silencing significantly mitigated HVR , independent of the blood pressure level. Ang II upregulated YAP expression and promoted YAP nuclear accumulation in a dose‐ and time‐dependent manner in rat VSMC s. YAP knockdown ameliorated Ang II ‐induced VSMC s phenotypic modulation. The regulation of YAP by Ang II could be blocked by pretreatment with angiotensin receptor type 1 antagonist losartan or F‐actin depolymerizing agent latrunculin B but not the AT 2R antagonist PD 123319. Disrupting the YAP ‐ TEA domain ( TEAD ) interaction with verteporfin inhibited Ang II ‐induced VSMC s phenotypic modulation. Conclusions Yes‐associated protein mediated angiotensin II ‐induced VSMC s phenotypic modulation and vascular remodelling. YAP is a potential therapeutic target for HVR beyond blood pressure control.