Yes-associated protein mediates angiotensin II-induced vascular smooth muscle cell phenotypic modulation and hypertensive vascular remodelling.
Cell Prolif
; 51(6): e12517, 2018 Dec.
Article
in En
| MEDLINE
| ID: mdl-30156340
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 (VSMCs) phenotypic modulation and to explore the underlying mechanisms. MATERIALS ANDMETHODS:
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-shRNA 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 VSMCs. YAP knockdown ameliorated Ang II-induced VSMCs 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 AT2R antagonist PD 123319. Disrupting the YAP-TEA domain (TEAD) interaction with verteporfin inhibited Ang II-induced VSMCs phenotypic modulation.CONCLUSIONS:
Yes-associated protein mediated angiotensin II-induced VSMCs phenotypic modulation and vascular remodelling. YAP is a potential therapeutic target for HVR beyond blood pressure control.
Full text:
1
Database:
MEDLINE
Main subject:
Pyridines
/
Angiotensin II
/
Apoptosis Regulatory Proteins
/
Vascular Remodeling
/
Imidazoles
/
Muscle, Smooth, Vascular
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Year:
2018
Type:
Article