Epigallocatechin-3-gallate Modulates Hyperglycemia-Triggered Macrophage Autophagy Through miR-204-5p Suppression: Implication for Acute Cardiometabloic Injury.

Epigallocatechin-3-gallate (EGCG) possess many biological properties. Autophagy and inflammation interact to cause cardiovascular diseases, and diabetic cardiovascular diseases; hyperglycemia- and hyperinsulinemia-induced microRNA reduction in the diabetic heart contribute to poor survival and increased infarct size in diabetic myocardial ischemia/reperfusion. However, whether EGCG affects macrophage autophagy and microRNA 204-5p (miR-204-5p) regulation under hyperglycemic conditions remain unclear. In this report, we investigated the effects of EGCG on the molecular regulatory mechanisms of miR-204-5p in LC3B macrophage autophagy under hyperglycemic stimulation conditions. Reverse transcription and real-time quantitative polymerase chain reaction, western blots, and luciferase activity assay were performed. Macrophages were cultured with 5.5 mM (low glucose) and 25 mM (high glucose) for hyperglycemia stimulation, and hyperglycemia was induced for 1 hour. EGCG attenuated cytoplasmic miR-204-5p levels under hyperglycemia stress in time-course and concentration dependent manners. Hyperglycemic treat-EGCG augmented the macrophage autophagy marker LCB mRNA by under hyperglycemia stress in a time-dependent manner significantly. Treatment with EGCG (10-5 M) or rapamycin or mutant miR-204-5p significantly augmented the LC3B protein expression through the suppressed miR-204-5p level in mouse macrophage cultures under high glucose (25 mM) stimulation at 6 hours. By luciferase activity assay, EGCG combined mutant miR-204-5p reduced LC3B binding activity under hyperglycemia stress. Taken together, EGCG regulates LC3B presentation under hyperglycemia stress by mediating the miR-204-5p under mimicking cardiometabolic injury. This study demonstrated that EGCG upregulated LC3B to suppress miR-204-5p expression in hyperglycemia-stimulated macrophage cultures. The results imply that EGCG is potentially effective for preventing hyperglycemia related cardiovascular diseases.