HO-1 activation can attenuate cardiomyocytic apoptosis via inhibition of NF-kappaB and AP-1 translocation following cardiac global ischemia and reperfusion.

Abstract

BACKGROUND NF-kappaB and AP-1 play important roles in regulation of inflammatory responses that lead to cardiomyocytic injury following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion. It has been reported that heme oxygenase-1 (HO-1) can block those responses. Our aim was to determine whether HO-1 activation could decrease myocardial ischemia-reperfusion injury with cardioplegia during CPB and attenuate apoptosis of cardiomyocytes. MATERIALS AND METHODS Rabbits (10 in each group) were randomized to receive either bypass only (Group 1), CPB plus intravenous normal saline (Group 2), hemin (HO-1 inducer; Group 3), SnPP (HO-1 inhibitor; Group 4), or hemin + SnPP (Group 5) 2 d before CPB. In all groups except Group 1, cold (4 degrees C) antegrade intermittent crystalloid cardioplegia was delivered every 20 min for a total of 60 min of cardiac arrest, after CPB was established. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points. The reperfused hearts were harvested for Western blotting and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) experiments. RESULTS The postoperative elevation of serum levels of IL-10, IL-6, and TNF-alpha were significantly decreased in Group 3, but HO-1 inhibitor abolished this effect (Group 4). Moreover in Group 3, the number of apoptotic cardiomyocytes, level of apoptosis-related activated fragments of caspase-3 and Akt, and level of nuclear NF-kappaB and AP-1 translocation were significantly decreased. CONCLUSIONS HO-1 activation can dampen the surge of inflammation-related cytokines during CPB and decrease the occurrence of cardiomyocytic apoptosis via inhibition of NF-kappaB and AP-1 translocation.

DOI: 10.1016/j.jss.2008.07.044

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@article{Yeh2009HO1AC, title={HO-1 activation can attenuate cardiomyocytic apoptosis via inhibition of NF-kappaB and AP-1 translocation following cardiac global ischemia and reperfusion.}, author={Chi-Hsiao Yeh and Tzu-Ping Chen and Yao-Chang Wang and Yu-Min Lin and Pyng Jing Lin}, journal={The Journal of surgical research}, year={2009}, volume={155 1}, pages={147-56} }