TNF-alpha induced cardiomyocyte apoptosis was associated with cardiac dysfunction caused by coronary microembolization

Backgrounds: This experimental study was designed to clarify the occurrence of cardiomyocyte apoptosis and its relation with Tumor Necrosis Factor-alpha (TNF-α) expression and cardiac function after Coronary Microembolization (CME). Methods: Fifteen mini-pigs were divided into Sham-operation group (n=4), CME group (n=6) and adalimumab pre-treatment group (n=5) (TNF-α antibody, 2mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and one week after procedure. Cardiomyocyte apoptosis was stained by TUNEL method, and caspase-3 and caspase-8 mRNA was detected by RT-PCR. Furthermore, serum TNF-α, IL-6 and troponin T were analyzed, while myocardial expressions of TNF-α and IL-6 were detected by western blot and immunohistochemistry. Results: TNF-α expression (serum level and myocardial expression) was significantly increased in CME group, and the average number of cardiomyocyte apoptosis nuclei was also higher than that in sham-operation group. Compared with sham-operation group, Left Ventricular End-Systolic Volume (LVESV) in CME group was increased at 6th hour after CME, while Left Ventricular Ejection Fraction (LVEF) was decreased. Pre-treatment with adalimumab not only significantly improved LVEF after CME, but also suppress the process of cardiomyocyte apoptosis and the mRNA expression of caspase-3 and caspase-8. Meanwhile, we found that average number of cardiomyocyte apoptosis nuclei had a negative relation with LVEF. Conclusions: TNF-α induced cardiomyocyte apoptosis could be involved in the cardiac dysfunction after CME. TNF-α antibody therapy could suppress cardiomyocyte apoptosis and improve early cardiac function after CME.