Back to Search
Start Over
The covalent NLRP3-inflammasome inhibitor Oridonin relieves myocardial infarction induced myocardial fibrosis and cardiac remodeling in mice
- Source :
- International Immunopharmacology. 90:107133
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Background Myocardial infarction (MI) triggers a strong inflammatory response that is associated with myocardial fibrosis and cardiac remodeling. Interleukin (IL)-1β and IL-18 are key players in this response and are controlled by NLRP3-inflammatory bodies. Oridonin is a newly reported NLRP3 inhibitor with strong anti-inflammatory activity. We hypothesized that the covalent NLRP3 inhibitor Oridonin could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in mice, improve poor heart remodeling, and preserve heart function. Methods Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and then treated with Oridonin (1, 3, or 6 mg/kg), MCC950 (10 mg/kg), CY-09 (5 mg/kg) or saline three times a week for two weeks. Four weeks after MI, cardiac function and myocardial fibrosis were assessed. In addition, myocardial expressions of inflammatory factors and fibrotic markers were analyzed by western blot, immunofluorescence, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. Results Oridonin treatment preserved left ventricular ejection fraction and fractional shortening, and markedly limited the myocardial infarct size in treated mice. The myocardial fibrosis was lower in the 1 mg/kg group (15.98 ± 1.64)%, 3 mg/kg group (17.39 ± 2.45)%, and 6 mg/kg group (16.76 ± 3.06)% compared to the control group (23.38 ± 1.65)%. Moreover, similar with the results of Oridonin, MCC950 and CY-09 also preserved cardiac function and reduced myocardial fibrosis. The expression levels of NLRP3, IL-1β and IL-18 were decreased in the Oridonin treatment group compared to non-treated group. In addition, myocardial macrophage and neutrophil influxes were attenuated in the Oridonin treated group. Conclusions The covalent NLRP3-inflammasome inhibitor Oridonin reduces myocardial fibrosis and preserves cardiac function in a mouse MI model, which indicates potential therapeutic effect of Oridonin on acute MI patients.
- Subjects :
- Male
0301 basic medicine
Inflammasomes
Neutrophils
Interleukin-1beta
Anti-Inflammatory Agents
Myocardial Infarction
Pharmacology
Ventricular Function, Left
0302 clinical medicine
Immunology and Allergy
Medicine
Myocytes, Cardiac
Sulfones
Myocardial infarction
Cells, Cultured
Receptors, Interleukin-18
Sulfonamides
Ejection fraction
Ventricular Remodeling
Interleukin
Indenes
Neutrophil Infiltration
030220 oncology & carcinogenesis
Thiazolidines
Diterpenes, Kaurane
Signal Transduction
Cardiac function curve
Immunology
Heterocyclic Compounds, 4 or More Rings
03 medical and health sciences
Left coronary artery
medicine.artery
NLR Family, Pyrin Domain-Containing 3 Protein
Animals
Furans
business.industry
Macrophages
Therapeutic effect
Thiones
Stroke Volume
medicine.disease
Fibrosis
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Myocardial fibrosis
Ligation
business
Subjects
Details
- ISSN :
- 15675769
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- International Immunopharmacology
- Accession number :
- edsair.doi.dedup.....2f027e46a0103861acce01b77f54b468