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


CONCLUSIONS
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.
Ge
G
Li-Sha
Chen
C
Yi-He
Zhou
Z
Na-Dan
Zhang
Z
Teng
Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. liyuechun1980@sina.com.
Li
L
Yue-Chun
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D050882:CREB-Binding Protein / Q000096:biosynthesis*; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014764:Viral Proteins / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014764:Viral Proteins; C097017:coxsackie B3 virus protein 2B; D000077261:Carvedilol; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse