Heart failure indicates that heart is ultimately unable to pump enough blood for the whole body. The mortality rate due to ischemic heart disease has not changed dramatically, but that for heart failure has risen steeply. However, molecular mechanism of development of heart failure is not fully elucidated.
We combined the microarray results of heart failure: AMI model, doxorubicin-induced heart failure, and the chronic heart failure patients. Among 5 genes commonly increased, we investigated the role of IPP2 in heart failure. αMHC promoter-IPP2 Transgenic mice (TgIPP2) were acquired and subjected to either left anterior descending artery ligation or repeated administration of doxorubicin. TgIPP2 mice showed a rapid decline in ejection fraction and fractional shortening. Cardiac function at the end of follow-up was lower than that of wild type littermate and the survival rate was also significantly reduced. Heart failure tends to be more severe in TgIPP2, but a much larger amount of myocardium in the infarction zone survived in TgIPP2.
In conclusion, IPP2 increased gene expression in both chemotherapy- and AMI-induced heart failure models, and the cardiac function of TgIPP2 mice rapidly deteriorated in both models of heart failure. In other words, IPP2 is a causative gene for heart failure and proper suppression of either IPP2 or substrate of IPP2 may be a new therapeutic concept to reduce heart failure transition.