Platycodin D (PD) attenuates myocardial apoptosis mediated by JNK-SIRT1-HSF1-IGF-IIR-Caspase-3 signaling in hypertensive conditions

Hypertension is a progressive condition. The compensatory left ventricular hypertrophy maintains cardiac output. It leads to myocardial remodeling characterized by fibrosis, insufficient vascularization, even apoptosis and heart failure. This condition involves a possible mechanism of Ang II-induced cardiac apoptosis through the activation of IGF-IIR by JNK-SIRT1-HSF1 regulation. In this study, we demonstrate that PD is capable of inhibiting IGF-IIR transcription and translation without cytotoxicity. These findings suggest that PD has an effect on IGF-IIR expression that is related to hypertension-induced apoptosis. Most important of all, PD reduces pHSF1 and pJNK expression induced by Ang II. SIRT1 expression is also upregulated by PD compared with the Ang II group. PD suppresses apoptosis, as indicated by reductions in Ang II-induced caspase-3 activity and IGF-IIR translocation to the cell membrane. These results indicate that PD may be a functional compound to protect cardiomyoblasts from apoptosis occurring in response to hypertension.