BET protein inhibition mitigates acute myocardial infarction damage in rats via the TLR4/TRAF6/NF-κB pathway.

摘要: Acute myocardial infarction (AMI) is among the most serious cardiovascular diseases and a leading cause of mortality in developed countries. Previous studies have indicated central role played by bromodomain (BRD) proteins, which belong to BRD extra-terminal (BET) family, gene control during heart failure pathogenesis. In addition, BET inhibition has been shown suppress cardiomyocyte hypertrophy. However, proteins remains unclear. The present study aimed investigate whether BETs mitigates AMI, explore molecular mechanism underlying this effect. A rat model acute was established, rats were divided into sham, AMI + JQ1 groups. JQ1, well-known selective inhibitor, used domain family activity. mRNA protein expression levels BRD2, BRD3 BRD4 evaluated using quantitative polymerase chain reaction western blot analysis, respectively. markers cardiac damage determined commercial kits. results that BRD2 significantly increased group compared with those sham group. decreased vivo reversing function injury, decreasing serum lactate dehydrogenase creatine kinase-MB isozyme activity, addition high-sensitivity C-reactive interleukin-6. Furthermore, suggested Toll-like receptor 4 (TLR4) signaling activated TLR4, TNF receptor-associated factor 6 (TRAF6) nuclear (NF)-κB AMI. treatment suppressed TLR4 activation. conclusion, demonstrated suppresses effect partially mediated TLR4/TRAF6/NF-κB signaling.