[Time course of myocardial NF-kappaB activation post coronary microembolization].
OBJECTIVE
To investigate the time course of myocardial NF-kappaB activation and association with cardiac function and other pro-inflammation cytokines following coronary microembolization (CME).


METHODS
CME was induced by homologous microthrombotic particle suspension injection into left ventricle with simultaneous short-term ascending aorta clamping. The CME rats were randomized to untreated group and pyrrolidine dithiocarbamate (PDTC, a specific NF-kappaB inhibitor) treated group (n = 32 respectively). The rats were sacrificed on day 1, 3, 7 and 14 post-operationally (n = 8 each). Twenty-four rats were sham-operated and served as controls. NF-kappaB DNA-binding activity was evaluated by electrophoretic mobility shift assay (EMSA), protein expressions of TNFalpha, IL-6 and ICAM-1 were analyzed by Western blotting, the dynamic alterations of TNFalpha, IL-6 and ICAM-1 mRNA were quantitatively assessed by Real-time PCR post hemodynamic measurements.


RESULTS
NF-kappaB DNA-binding activity in CME group was significantly increased than that of sham group on day 1, peaked at day 3 and was similar as that in sham rats on day 14. The protein and mRNA expressions of TNFalpha, IL-6 and ICAM-1 were significantly increased in CME group at various time points compared those in sham rats. NF-kappaB DNA-binding activity positively correlated with mRNA expressions of TNFalpha, IL-6, ICAM-1, respectively (r = 0.72, P < 0.05; r = 0.94, P < 0.01; r = 0.62, P < 0.05). PDTC significantly suppressed protein and mRNA expressions of TNFalpha, IL-6 and ICAM-1 (P < 0.05) and improved left ventricular function.


CONCLUSIONS
NF-kappaB activation post CME could upregulate the gene transcriptions of TNFalpha, IL-6, ICAM-1 and enhance inflammatory responses and aggravate left ventricular dysfunction.
Li
Shu-mei
SM
Department of Cardiology, Union Hospital, Fujian Medical University, Provincial Institute of Coronary Disease, Fuzhou 350001, China.
Zeng
Kai
K
Wang
Wei-wei
WW
Zhang
Fei-long
FL
Sun
Xu-dong
XD
Chen
Liang-long
LL
D000818:Animals; D003328:Coronary Thrombosis / Q000378:metabolism*; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1