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Exp Clin Endocrinol Diabetes 2021; 129(05): 339-348
DOI: 10.1055/a-1010-5543
Article

Enhanced Inflammatory Reaction and Thrombosis in High-Fat Diet-Fed ApoE-/- Mice are Attenuated by Celastrol

Mao Ouyang
1   Department of Geriatrics, the Third Xiangya Hospital, Central South University, Changsha, P. R. China
,
Tao Qin
1   Department of Geriatrics, the Third Xiangya Hospital, Central South University, Changsha, P. R. China
,
Hengdao Liu
1   Department of Geriatrics, the Third Xiangya Hospital, Central South University, Changsha, P. R. China
2   Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China
,
Junya Lu
1   Department of Geriatrics, the Third Xiangya Hospital, Central South University, Changsha, P. R. China
,
Caixia Peng
1   Department of Geriatrics, the Third Xiangya Hospital, Central South University, Changsha, P. R. China
,
Qin Guo
3   Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, P. R. China
› Author Affiliations Funding: This research was supported by the Key program of the Science-Technology Program of Hunan Province, China (Grant No. 2015JC3133).
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Abstract

Objective High-fat diet (HFD) increases the risk of inflammatory reaction and acute arterial thrombosis. Celastrol has been confirmed to regulate inflammatory cytokine levels in atherosclerotic animal models. However, the anti-thrombotic effects of celastrol have remained to be fully demonstrated. The present study was performed to investigate the beneficial effect of celastrol in HFD-induced inflammatory reaction and thrombosis in apolipoprotein (apo)E-/- mice.

Materials and Methods Thrombogenic mice model was established using HFD-fed apoE-/- mice. The levels of mRNA and protein were assayed by RT-qPCR and western blotting, respectively. Immunohistochemistry (IHC) staining was performed to measure the protein expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the aortic endothelium of HFD-fed apoE-/- mice.

Results The results demonstrated that the effect of HFD on inflammatory cytokines in mice with apoE-/- background was reversed by celastrol administration, and celastrol treatment inhibited the NOD-like receptor family, pyrin domain containing 3 (NLRP3)/caspase-1/interleukin-1β signaling cascades in peripheral blood mononuclear cells from HFD-fed apoE-/- mice. In addition, HFD enhanced adenosine diphosphate-induced platelet aggregation in normal C57BL/6 and apoE-/- mice, while celastrol administration reversed this. Furthermore, celastrol inhibited the pro-thrombotic effects of HFD in apoE-/- mice, and the underlying mechanism was mediated, at least partially, through the suppression of matrix metalloproteinase-2 and -9 expression.

Conclusions Celastrol administration significantly attenuated HFD-induced inflammatory reaction, platelet aggregation and thrombosis in apoE-/- mice, and celastrol may be used as a drug for the prevention of HFD-induced inflammatory reaction and thrombus.

Key words

thrombus - inflammation - celastrol - matrix metalloproteinase - NLRP3


Publication History

Received: 15 July 2019
Received: 18 August 2019

Accepted: 09 September 2019

Article published online:
16 March 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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