Targeting inhibition of HMGB3 protein transposition in cardiac mitochondria to improve myocardial ischemia reperfusion injury

Background Myocardial infarction (MI), as a manifestation of acute myocardial ischemia of coronary heart disease. The aim of this study is to search for the new targets and intervention strategy for MI. Methods 1242 MI patients and healthy people were enrolled from four medical centers. Proteomics technique was used to analyze the differential expressed proteins (DEPs) between AMI patients and healthy people. The effect and intervention effect of DEPs were investigated with gene knockout mice hypoxia/reoxygenation (H/R) cell and mitochondrial targeted siRNA. 4628 proteins and 365 DEPs were identified in MIT. Results High mobility group protein B3 (HMGB3) was the most obvious DEP, which was up-regulated in AMI patients compared with healthy people. Knockout or silence of HMGB3 canceled the effects of HMGB3. Triphenylphosphine (TPP)-HMGB3-siRNA (TPP-MIT-HMGB3-siRNA) could directly target myocardial mitochondria and intervene the myocardial dysfunction caused by HMGB3. Conclusions HMGB3 is an important biomarker and plays a critical role in acute myocardial ischemia/reperfusion (I/R) injury. TPP-MIT-HMGB3-siRNA is a powerful mean to intervene acute myocardial ischemic injury.