[Effects of pravastatin on myocardial connexin 43, IFN-gamma and IL-10 expressions in a murine model of viral myocarditis induced by Coxsackievirus B3].
OBJECTIVE
To observe the effects of pravastatin on myocardial connexin 43 (Cx43), IFN-gamma and IL-10 expressions in a murine model of viral myocarditis (VMC) induced by Coxsackievirus B3.


METHODS
Four-week-old male Balb/c mice were inoculated intraperitoneally with Coxsackievirus B3 and then randomly received saline (group A, n = 12), low dose pravastatin (40 mg.kg(-1).d(-1), group B, n = 12) and high dose pravastatin (80 mg.kg(-1).d(-1), group C, n = 12) for 14 days. Another group of mice were injected with Eagle's solution and treated with saline (group D, n = 12) or high dose pravastatin (80 mg.kg(-1).d(-1), group E, n = 12). After 14 days treatments, serum IFN-gamma, IL-10 were assayed using ELISA, myocardium IFN-gamma, IL-10 and Cx43 mRNA levels were measured by real-time PCR, myocardium expression of Cx43 was also determined by immunohistochemistry staining method on cardiac myocytes.


RESULTS
Pravastatin dose-dependently upregulated Cx43 proteins on membrane of myocardial cells (group A: 0.16 +/- 0.06, group B: 4.55 +/- 0.73 and group C: 5.21 +/- 0.42, P < 0.01 vs. group A) and Cx43 mRNA expression (group A: 1.000 +/- 0.127, group B: 1.320 +/- 0.096, group C: 1.550 +/- 0.126, P < 0.05 vs. group A), IL-10 mRNA expression (group A: 1.000 +/- 0.031, group B: 1.810 +/- 0.029, group C: 2.140 +/- 0.032, P < 0.05 vs. group A) while down-regulated IFN-gamma mRNA (group A: 1.000 +/- 0.061, group B: 0.603 +/- 0.063, group C: 0.333 +/- 0.071, P < 0.01 vs. group A). Serum IFN-gamma, IL-10 concentrations changed in the same direction as myocardial mRNA levels of IFN-gamma, IL-10 post pravastatin treatments.


CONCLUSIONS
Pravastatin treatments upregulated expressions of Cx43 at mRNA and protein levels and improved the INF-gamma/IL-10 balance which might be the working mechanisms for pravastatin-mediated anti-VMC and anti-arrhythmia effects in this VMC model.
Wu
Shi-Yao
SY
Department of Cardiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Fang
He-Ying
HY
D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D009206:Myocardium / Q000378:metabolism; D017035:Pravastatin / Q000627:therapeutic use*
D018031:Connexin 43; D016753:Interleukin-10; D007371:Interferon-gamma; D017035:Pravastatin