Tollip Negatively Regulates Vascular Smooth Muscle Cell–Mediated Neointima Formation by Suppressing Akt‐Dependent Signaling

Author:

Zhi Hong1,Gong Fu‐Han234,Cheng Wen‐Lin234,Zhu Kongbo1,Chen Long1,Yao Yuyu1,Ye Xingzhou1,Zhu Xue‐Yong234,Li Hongliang234

Affiliation:

1. Department of Cardiology Zhongda Hospital Affiliated to Southeast University Nanjing China

2. Department of Cardiology Renmin Hospital of Wuhan University Wuhan China

3. Basic Medical School Wuhan University Wuhan China

4. Institute of Model Animal of Wuhan University Wuhan China

Abstract

Background Tollip, a well‐established endogenous modulator of Toll‐like receptor signaling, is involved in cardiovascular diseases. The aim of this study was to investigate the role of Tollip in neointima formation and its associated mechanisms. Methods and Results In this study, transient increases in Tollip expression were observed in platelet‐derived growth factor‐ BB –treated vascular smooth muscle cells and following vascular injury in mice. We then applied loss‐of‐function and gain‐of‐function approaches to elucidate the effects of Tollip on neointima formation. While exaggerated neointima formation was observed in Tollip‐deficient murine neointima formation models, Tollip overexpression alleviated vascular injury–induced neointima formation by preventing vascular smooth muscle cell proliferation, dedifferentiation, and migration. Mechanistically, we demonstrated that Tollip overexpression may exert a protective role in the vasculature by suppressing Akt‐dependent signaling, which was further confirmed in rescue experiments using the Akt‐specific inhibitor ( AKTI ). Conclusions Our findings indicate that Tollip protects against neointima formation by negatively regulating vascular smooth muscle cell proliferation, dedifferentiation, and migration in an Akt‐dependent manner. Upregulation of Tollip may be a promising strategy for treating vascular remodeling–related diseases.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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