Valsartan protects against ER stress-induced myocardial apoptosis via CHOP/Puma signaling pathway in streptozotocin-induced diabetic rats

Tingting Wu, Zhe Dong, Jing Geng, Yingying Sun, Guanghui Liu, Weiqiang Kang, Yun Zhang, Zhiming Ge
European Journal of Pharmaceutical Sciences 2011 April 18, 42 (5): 496-502
Recently studies indicated that valsartan could prevent the progression of heart failure caused by diabetic cardiomyopathy (DCM), while the mechanisms were still poorly understood. The present study was designed to investigate whether valsartan could reduce the endoplasmic reticulum (ER) stress and DCM-induced cardiac remodeling. Our data has shown that valsartan can ameliorate ER stress-induced cardiac remodeling and myocardial apoptosis in DCM rats. By using of immunofluorescence and RT-PCR, valsartan has been found to play a protective role via down-regulating the expression of transcriptional induction of C/EBP homologous protein (CHOP) and p53 upregulated modulator of apoptosis (Puma), two crucial factors known to be implicated in the ER stress-induced myocardial apoptosis. And the expression level of Puma was closely related to CHOP. Thus, our experiment strongly suggests that the administration of valsartan can ameliorate the ER stress through blocking the activation of CHOP/Puma signaling pathway, which provides a new insight into the potential molecular mechanism of cardiomyocyte apoptosis.

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