Effects of carvedilol treatment on cardiac cAMP response element binding protein expression and phosphorylation in acute coxsackievirus B3-induced myocarditis

BMC Cardiovascular Disorders

Li Yue-Chun²  Zhang Teng²  Zhou Na-Dan²  Chen Yi-He²  Ge Li-Sha¹ 

[1] Department of Pediatric, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China;Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China

关键词: Carvedilol;    cAMP response element binding protein;    Viral myocarditis;   

Others  :  856687
DOI  :  10.1186/1471-2261-13-100

 received in 2013-08-18, accepted in 2013-11-12,  发布年份 2013

【 摘 要 】

Background

The role of β-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of β-adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective β-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis.

Methods

This study was therefore designed to examine the effects of carvedilol on the transcriptional factor CREB in a murine model of acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol on plasma noradrenaline, heart rate and blood pressure, myocardial histopathological changes and fibrosis, cardiomyocyte apoptosis, cardiac CREB and phosphorylated CREB, cytokine levels, and viral RNA were studied.

Results

The expression and phosphorylation of CREB were decreased with concomitant increase of IL-6 and TNF-α in murine coxsackievirus-induced acute viral myocarditis. The levels of IL-6 and TNF-α were correlated with the expression of CREB or phosphorylated CREB. Carvedilol increased the cardiac CREB expression and phosphorylation and decreased the plasma catecholamine levels and the production of IL-6 and TNF-α with amelioration of acute viral myocarditis.

Conclusion

These results show that CREB may be involved in the pathophysiology of viral myocarditis and carvedilol exerts some of its beneficial effects by increasing the CREB expression and phosphorylation.

【 授权许可】

   
2013 Li-Sha et al.; licensee BioMed Central Ltd.

【 图 表 】

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