ReferenceID 4943
Colchicine Ameliorates Dilated Cardiomyopathy Via SIRT2-Mediated Suppression of NLRP3 Inflammasome Activation
J Am Heart Assoc
Background Dilated cardiomyopathy remains a leading cause of heart failure worldwide. Immune inflammation response is recognized as a significant player in the progression of heart failure; however, immunomodulatory stra
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- Reference Id
- 4943
- Evidence Id
- 21533
- Core Evidence Id
- 21533
- Source Reference Id
- 3142
- Herb2 Reference Id
- HBREF003939
- Subject Paper Key
- HBIN021260_35766262
- Pubmed Id
- 35766262
- Doi
- 10.1161/JAHA.122.025266
- Paper Title
- Colchicine Ameliorates Dilated Cardiomyopathy Via SIRT2-Mediated Suppression of NLRP3 Inflammasome Activation
- Paper Abstract
- Background Dilated cardiomyopathy remains a leading cause of heart failure worldwide. Immune inflammation response is recognized as a significant player in the progression of heart failure; however, immunomodulatory strategies remain a long-term challenge. Colchicine, a potent anti-inflammatory drug, has many benefits in ischemic cardiovascular events, but its role in nonischemic heart failure remains unclear. Methods and Results Doxorubicin administration was used to establish a murine dilated cardiomyopathy model, and colchicine or saline was orally given. At the end point, cardiac function and fibrosis were measured to investigate the effects of colchicine. Inflammatory cytokine levels, neutrophil recruitment, and NLRP3 (NOD-like receptor protein 3) inflammasome activation were detected to evaluate the inflammatory response. Furthermore, to examine the downstream target of colchicine, SIRT2 (Sirtuin 2) was pharmacologically inhibited in vitro; thus, changes in the NLRP3 inflammasome were detected by immunoblotting. These results showed that murine cardiac function was significantly improved and fibrosis was significantly alleviated after colchicine treatment. Moreover, the infiltration of neutrophils and the levels of inflammatory cytokines in the failing myocardium were both decreased by colchicine treatment. Mechanistically, colchicine upregulated the expression of SIRT2, leading to the inactivation of the NLRP3 inflammasome in an NLRP3 deacetylated manner. Conversely, the inhibition of SIRT2 attenuated the suppressive effect of colchicine on NLRP3 inflammasome activation. Conclusions This study indicated that colchicine could be a promising therapeutic candidate for dilated cardiomyopathy and other nonischemic heart failure associated with the inflammatory response.
- Journal
- J Am Heart Assoc
- Publish Year
- 2022
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Heart Failure; Dilated Cardiomyopathy; Fibrosis; Nonischemic Heart Failure
- Paper Title Cn
- Paper Title En
- Colchicine Ameliorates Dilated Cardiomyopathy Via SIRT2-Mediated Suppression of NLRP3 Inflammasome Activation
- Bilingual Status
- semi_complete