Immunomodulation by atorvastatin upregulates expression of gap junction proteins in coxsackievirus B3 (CVB3)-induced myocarditis.
OBJECTIVE
To investigate the effect of atorvastatin on myocardial expression of gap junction proteins, connexins (Cxs), during coxsackievirus B3 (CVB3)-induced myocarditis.


METHODS
Viral myocarditis was induced in mice by inoculation with CVB3. Atorvastatin (5 or 10 mg kg(-1) day(-1)) or saline was administered by daily oral gavage from the day of induction of viral myocarditis to the day of sacrifice. Fourteen days after injection of CVB3, animals were sacrificed. Alterations in myocardial Cxs expression were examined by RT-PCR, immunoblot, and immunohistochemistry. Plasma levels of TNF-alpha and IFN-gamma were measured by ELISA.


RESULTS
Fourteen days after inoculation with CVB3, myocardial expression of Cx43 and Cx45 was significantly downregulated. Treatment with atorvastatin not only reduced the overproduction of TNF-alpha and IFN-gamma, but also enhanced the expression of Cx43 and Cx45, therefore attenuating myocardial injury and improving the survival rate of viral myocarditis.


CONCLUSIONS
This study shows for the first time that myocardial expression of Cxs is downregulated during CVB3-induced myocarditis and that immunomodulation by atorvastatin could restore the impaired gap junction channels and improve the outcome of viral myocarditis.
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Alian
A
Zhang
Huili
H
Zhang
Shiyao
S
Wu
D000818:Animals; D000069059:Atorvastatin; D015153:Blotting, Western; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D003384:Coxsackievirus Infections / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006538:Heptanoic Acids / Q000494:pharmacology*; D007150:Immunohistochemistry; D007155:Immunologic Factors; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009205:Myocarditis / Q000378:metabolism* / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D018031:Connexin 43; D017630:Connexins; D016207:Cytokines; D006538:Heptanoic Acids; D007155:Immunologic Factors; D011758:Pyrroles; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C082920:connexin 45; D007371:Interferon-gamma; D000069059:Atorvastatin