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Tollip Negatively Regulates Vascular Smooth Muscle Cell-Mediated Neointima Formation by Suppressing Akt-Dependent Signaling.


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.

SUBMITTER: Zhi H 

PROVIDER: S-EPMC6220530 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Tollip Negatively Regulates Vascular Smooth Muscle Cell-Mediated Neointima Formation by Suppressing Akt-Dependent Signaling.

Zhi Hong H   Gong Fu-Han FH   Cheng Wen-Lin WL   Zhu Kongbo K   Chen Long L   Yao Yuyu Y   Ye Xingzhou X   Zhu Xue-Yong XY   Li Hongliang H  

Journal of the American Heart Association 20180610 12


<h4>Background</h4>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.<h4>Methods and results</h4>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  ...[more]

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