Inhibition of JNK and p38 MAPK ‐mediated inflammation and apoptosis by ivabradine improves cardiac function in streptozotocin‐induced diabetic cardiomyopathy

This study investigated whether ivabradine exerts a therapeutic effect in DCM. C57BL/6J mice were injected intraperitoneally with streptozotocin (STZ) to induce diabetes; then administered with ivabradine or saline (control). After 12 weeks, the surviving mice were analyzed to determine the cardioprotective effect of ivabradine against DCM. Although treatment with ivabradine did not affect blood glucose levels, it attenuated tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6 messenger RNA (mRNA) expression, inhibi ted c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (p38 MAPK) activation, reduced histological abnormalities, myocardial apoptosis and collagen deposition, and improved cardiac function in the diabetic mice. Interestingly, the anti‐inflammatory and antiapoptotic prope rties of ivabradine, but not its inhibitory effect on JNK and p38 MAPK, were observed in high‐glucose‐cultured neonatal rat ventricular cardiomyocytes. Attenuating inflammation and apoptosis via intramyocardial injection of lentiviruses carrying short hairpin RNA targeting JNK and p38 MAPK vali dated that the anti‐inflammatory and antiapoptotic effects of ivabradine were partly attributed to JNK and p38 MAPK inactivation in diabetic mice. In summary, these data indicate that ivabradine‐mediated improvement of cardiac function in STZ‐induced diabetic mice may be partly attributed to i nhibition of JNK/p38 MAPK‐mediated inflammation and apoptos...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research