Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPKSIRT1 Pathway
Joint Authors
Zhang, Ruoxi
Huang, Xingtao
Yang, Mengyue
Lv, Hang
Liu, Qi
Zhang, Lu
Wang, Xuedong
Han, Baihe
Hou, Shenglong
Liu, Dandan
Wang, Gang
Yu, Bo
Hou, Jingbo
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-15
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
Cholesterol crystal- (CC-) induced endothelial cell inflammation and pyroptosis play an important role in the development of cardiovascular diseases, especially in atherosclerosis (AS).
Increasing evidence suggests that cholesterol crystals are known to be a pivotal pathological marker of atherosclerotic plaque vulnerability.
As a classical nonspecific anti-inflammatory drug, colchicine has been widely used in the treatment of acute gout.
However, whether colchicine could alleviate CC-induced endothelial cell injury and the related mechanisms remains to be addressed.
In this study, the protective effect of colchicine on human umbilical vein endothelial cells (HUVECs) was confirmed.
Our results revealed that after cotreatment with colchicine and cholesterol crystals in endothelial cells, the uptake of cholesterol crystals was significantly decreased, the cell viability was obviously increased, and the release of lactate dehydrogenase (LDH) and the number of pyroptotic cells decreased significantly; then, the expression of NLRP3 inflammasome-related proteins and various inflammatory factors was also visibly suppressed; moreover, as a potent activator of NLRP3 inflammasome, the intracellular ROS level was clearly reduced, while mitochondrial membrane potential improved significantly.
In addition, the expression levels of AMP-dependent kinase (AMPK) pathway-related proteins as well as various antioxidant enzymes were elevated notably in varying degrees.
However, the above effects of colchicine were completely offset by the treatment of siRNA targeting AMPKα and Sirtuin1 (SIRT1).
Therefore, we conclude that colchicine plays a crucial role in alleviating the intracellular inflammatory response and NLRP3 inflammation activation, attenuating the levels of cellular oxidative stress and pyroptosis in endothelial cells via regulating AMPK/SIRT1 signaling, which may be a concrete mechanism for the secondary prevention of cardiovascular diseases.
American Psychological Association (APA)
Yang, Mengyue& Lv, Hang& Liu, Qi& Zhang, Lu& Zhang, Ruoxi& Huang, Xingtao…[et al.]. 2020. Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPKSIRT1 Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-18.
https://search.emarefa.net/detail/BIM-1205966
Modern Language Association (MLA)
Yang, Mengyue…[et al.]. Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPKSIRT1 Pathway. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-18.
https://search.emarefa.net/detail/BIM-1205966
American Medical Association (AMA)
Yang, Mengyue& Lv, Hang& Liu, Qi& Zhang, Lu& Zhang, Ruoxi& Huang, Xingtao…[et al.]. Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPKSIRT1 Pathway. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-18.
https://search.emarefa.net/detail/BIM-1205966
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205966