Objectives Heart failure is the leading cause of death in patients with chronic kidney disease (CKD). Advanced oxidation protein products (AOPPs) induced microvascular pathology and contributed to the pathogenesis of CKD. We investigated whether cardiomyocyte apoptosis was induced by AOPPs in CKD.
Methods CKD models were established in Sprague-Dawley rats. The serum levels of AOPPs were tested and the cardiomyocyte apoptosis in cardiac sections were calculated. In vitro, H9C2 rat cardiomyoblast cells were treated with AOPPs and NADPH oxidase inhibitor apocynin. And then, the apoptosis of H9C2 rat cardiomyoblast cells and the expression of cleaved caspase-3 were tested. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) was tested in vitro.
Results Compared with those in sham-operated rats, the serum levels of AOPPs significantly increased (40.48 ± 3.08 μmol/L in sham-operated rats vs. 104.70 ± 7.66 μmol/L in CKD rats, P < 0.05) and correlated well with the levels of cardiomyocyte apoptosis in CKD rats. In H9C2 rat cardiomyoblast cells, the apoptotic effect of AOPPs was significantly attenuated by a NADPH oxidase inhibitor, apocynin. Moreover, we found that this inhibitory effect was mediated by reducing the phosphorylation of JNK pathway.
Conclusions Our results suggested that AOPPs could promote cardiomyocyte apoptosis in CKD, which is likely mediated by the activation of NADPH oxidase and phosphorylation of JNK pathway was involved in this process