Background
( -)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol isolated from green tea, has recently garnered attention for its potential protective role against acute myocardial infarction (MI) via inhibiting inflammation. Herein, we tested whether EGCG participates in modulating cardiac ischemia reperfusion-induced injury and elucidate its potential mechanisms.
Conclusion
EGCG protected cardiomyocytes from pyroptosis by the MEG3/TAF15/AIM2 axis, indicating EGCG as a potential novel therapeutic strategy for managing MI.
Methods
To induce MI in mice, we employed coronary artery ligation, while cell models utilized oxygen glucose deprivation/re-oxygenation (OGD/R)-treated HL-1 cells. TTC, HE and Massion staining evaluated the pathological changes of heart tissues. Besides, RNA-pull down and RIP assays analyzed the interactions of MEG3/TAF15 and AIM2 mRNA/TAF15. FISH associated with immunofiuorescence (IF) double staining was conducted to measure the co-localization of MEG3 and TAF15.
Results
In vitro and in vivo evidence supported that EGCG treatment improved cardiomyocytes viability while inhibiting the expressions of AIM2, C-caspase-1, ASC, GSDMD-N, IL-18 and IL-1β. Knockdown of MEG3 intensified EGCG's therapeutic effects both in vitro and in vivo. LncRNA MEG3 and AIM2 mRNA interacted with TAF15, and MEG3, in turn, promoted the stability of AIM2 mRNA through regulating TAF15. Overexpression of TAF15 reversed the promoting effect of EGCG and MEG3 knockdown on cell viability, and the inhibiting effect on cell pyroptosis.