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Article

Carvedilol alleviates diabetic cardiomyopathy in diabetic rats

  • Authors:
    • Wencheng Zheng
    • Ding Li
    • Xiang Gao
    • Wenqian Zhang
    • Barry O. Robinson
  • View Affiliations / Copyright

    Affiliations: Fourth Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Department of Cardiac Electrophysiology, Peking University People's Hospital, Peking University, Beijing 100044, P.R. China, First Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Department of Non‑Invasive Cardiovascular Services, Brookwood Health Hospital, Birmingham, AL 35211, USA
  • Pages: 479-487
    |
    Published online on: November 12, 2018
       https://doi.org/10.3892/etm.2018.6954
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Abstract

Diabetic cardiomyopathy (DCM) is characterized by structural and functional changes in the myocardium. Several studies have revealed that myocardial apoptosis and fibrosis occur during DCM. Studies have also indicated that oxidative stress may be a major factor associated with the development of DCM. Protein kinase C (PKC)β2 has been demonstrated to be activated in diabetic rats, and overexpression of PKCβ2 in the myocardium may result in cardiac hypertrophy and fibrosis. The P66shc adaptor protein, which is mediated by PKCβ, serves an important role in apoptosis during oxidative stress. The aim of the present study was to investigate whether the PKCβ2/P66shc oxidative stress pathway is associated with DCM, and to investigate the role and mechanisms of carvedilol in preserving cardiac function. Experimental diabetic rat models were induced by streptozotocin treatment accompanied by high energy intake. Carvedilol was orally administrated at a dose of 1 or 10 mg/kg/day. Cardiac function was evaluated by serum N‑terminal pro‑B‑type natriuretic peptide level and cardiac ultrasound. Myocardial inflammation, oxidative stress, apoptosis and fibrosis were assessed by histopathological and echocardiographic analyses and tests for oxidative markers. Associated proteins and factors were examined by immunohistochemical and western blot analyses. Rats in the diabetes mellitus group exhibited significantly decreased systolic cardiac function along with elevated expression levels of phosphorylated (p)‑PKCβ2, phos‑P66shc, caspase‑3, malondialdehyde, collagen type I, tumor necrosis factor‑α and interleukin‑1β, which were accompanied by disorder in metabolic processes. Treatment with carvedilol reversed these changes. Thus, the present results suggest that the PKCβ2/P66shc signaling pathway may be associated with diabetic cardiomyopathy; furthermore, carvedilol, as a novel β‑receptor blocker, may protect the myocardium from injury by suppressing the myocardial inflammatory response, fibrosis, P66shc‑mediated oxidative stress and subsequent apoptosis in myocardial tissue. Consequently, carvedilol may have potential as a therapy for the treatment of DCM.
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Copy and paste a formatted citation
Spandidos Publications style
Zheng W, Li D, Gao X, Zhang W and Robinson BO: Carvedilol alleviates diabetic cardiomyopathy in diabetic rats. Exp Ther Med 17: 479-487, 2019.
APA
Zheng, W., Li, D., Gao, X., Zhang, W., & Robinson, B.O. (2019). Carvedilol alleviates diabetic cardiomyopathy in diabetic rats. Experimental and Therapeutic Medicine, 17, 479-487. https://doi.org/10.3892/etm.2018.6954
MLA
Zheng, W., Li, D., Gao, X., Zhang, W., Robinson, B. O."Carvedilol alleviates diabetic cardiomyopathy in diabetic rats". Experimental and Therapeutic Medicine 17.1 (2019): 479-487.
Chicago
Zheng, W., Li, D., Gao, X., Zhang, W., Robinson, B. O."Carvedilol alleviates diabetic cardiomyopathy in diabetic rats". Experimental and Therapeutic Medicine 17, no. 1 (2019): 479-487. https://doi.org/10.3892/etm.2018.6954
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng W, Li D, Gao X, Zhang W and Robinson BO: Carvedilol alleviates diabetic cardiomyopathy in diabetic rats. Exp Ther Med 17: 479-487, 2019.
APA
Zheng, W., Li, D., Gao, X., Zhang, W., & Robinson, B.O. (2019). Carvedilol alleviates diabetic cardiomyopathy in diabetic rats. Experimental and Therapeutic Medicine, 17, 479-487. https://doi.org/10.3892/etm.2018.6954
MLA
Zheng, W., Li, D., Gao, X., Zhang, W., Robinson, B. O."Carvedilol alleviates diabetic cardiomyopathy in diabetic rats". Experimental and Therapeutic Medicine 17.1 (2019): 479-487.
Chicago
Zheng, W., Li, D., Gao, X., Zhang, W., Robinson, B. O."Carvedilol alleviates diabetic cardiomyopathy in diabetic rats". Experimental and Therapeutic Medicine 17, no. 1 (2019): 479-487. https://doi.org/10.3892/etm.2018.6954
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