Objective Using intravenous injection of adeno-associated virus serotypes 9 carring ribozyme gene (AAV9-R65), we examined whether inhibition NF-κB would prevent post-infarct left ventricular rupture and remodelling in aged mice.
Methods and results Old (18-month-old) C57BL/6 male mice were given AAV9-R65 by tail vein injection 16 days before operation (MI+R65). Myocardial infarction was induced by ligation of the left coronary artery in MI+R65 group and myocardial infarction (MI) group mice. NF-κB activity was inhibited in MI+R65 mice. Inhibition of NF-κB reduced cardiac rupture in MI+R65 group (15.2% vs 32.8%, p=0.018). Echocardiographic measurements revealed that diameter of LV was significantly decreased, and ventricular wall thickness, fraction shortening were significantly increased in MI+R65 mice compared with MI mice (p<0.05). MMP-9 and TNF-α were decreased in MI+R65 group (p<0.05). And collagen was also decreased in MI+R65 group (p<0.05). But there were no changes of IL-1β in MI+R65 group.
Conclusions Cardiac rupture and remodelling were attenuated in aged mice by ribozyme gene transfer with adeno-associated virus serotypes 9. It maybe caused by decreased collagen as the result of decreased MMP-9, TNF-α which proved that NF-κB signal pathway may be associated with cardiac rupture and remodelling in aged mice.