Abstract 568: Effects of Burn-induced Cardiac Released Factors on Cardiomyocyte and Profiles of Differentially Expressed Cardiac Mitochondrial Proteins Effects of Burn-induced Cardiac Released Factors on Cardiomyocyte and Profiles of Differentially Expressed Cardiac Mitochondrial Proteins

Abstract

Introduction: Previous studies have indicated that cardiac dysfunction worsens in the first 24 hours post burn (pb) and improved over the next 48 hpb. We have found that cardiac mitochondria were damaged at 24 hpb and 24 hpb serum-treatment caused cardiomyocyte’mitochondrial dysfunction. However, the differentially expression of mitochondrial proteins in the early post burn period have still not been explored. Aims: To test if 3 hpb serum-treatment will interfere cardiomyocyte growth/proliferation similar to 24 hpb serum-treatment in vitro ; To identify the cardiac mitochondrial protein expression profile, relating to burn-induced cardiac mit dysfunction. Methods: Male Sprague Dawley rats were randomized into sham control, 3 hpb and 24 hpb groups, with six rats in each group. 60% TBSA burn was induced by immersing in boiling water. In this study, heart function cardiac mit function, and cardiac mitochondrial protein profiles were measured. Burned rat serum were used to test our hypothesis in vitro . Results: Cardiac functions was significantly worse in 3 hpb (Fig 1). Cardiac mitochondrial dysfunction was observed via mit OXPHOS or mit complexes activities after burn. However, no change of CII-driving OXPHOS in 24 hpb and no change of CIII activity in 3 hpb were seen, suggesting that different mechanisms may be involved (Fig.2). Burn-serum treatment increased oxidative stress, apoptosis, and nitrite/nitrate, while decreasing antioxidants and cell proliferation in cardiomyocytes (Fig. 3). Nano LC MS/MS identified 13569 peptides and 1275 proteins from burn-induced heart lysates (Fig.4.A), which were associated with cardiomyopathy (Fig.4.B). Further analysis showed that burn injury induced the alterations of 25 up regulated signaling pathway and 7 down regulated signaling pathway (Fig.5.A). 147 mitochondrial proteins were identified to be differentially expressed after burn. Among the 147 proteins, 32 proteins were continually down-regulated, 37 continually up-regulated. In addition, 16 were first up regulated then down-regulated while38 had the opposite expression perform (Fig.5.B). Conclusions: Burn-induced heart dysfunction is associated with cardiac mitochondrial damage by altering mitochondrial protein expression.