Protective effects of losartan in mice with chronic viral myocarditis induced by coxsackievirus B3
2013
Zhang, Yuan-Yuan | Li, Jin-Nan | Xia, Harry Hua-Xiang | Zhang, Shi-Lun | Zhong, Jiang | Wu, Yi-Ying | Miao, Shi-Kun | Zhou, Li-Ming
AIM: To investigate whether losartan has protective effects in mice with chronic viral myocarditis induced by coxsackievirus B3 (CVB3). MAIN METHODS: Thirty two male Balb/c mice were intraperitoneally injected with CVB3 (10×TCID₅₀) to induce chronic viral myocarditis (CVM). Losartan at 12.5mg/kg (n=16) or normal saline (n=16) were orally administered daily for 28days to these mice. Uninfected mice (n=6) were used as controls. On day 29, all mice underwent anesthesia and echocardiography prior to sacrifice. Serum IL-17, IL-4, IFN-γ and TNF-α levels were measured by enzyme-linked immunosorbent assay, and cardiac tissues were histologically examined after hematoxylin & eosin staining. In addition, the effect of losartan on the virus titers in primary cultured neonatal rat cardiomyocytes infected with CVB3 was measured on Hep-2 cells at 72h post infection. KEY FINDINGS: Mice infected with CBV3 had significantly increased mortality, heart/body weight ratios, necrosis and inflammatory scores and decreased cardiac ejection fractions, compared with the controls (all P<0.05). Losartan significantly decreased mortality from 40.0% to 12.5%, heart/body weight ratios from 7.08±2.17 to 4.15±0.99, and necrosis and inflammatory scores from 3.33±0.50 to 2.50±0.65 (all P<0.05), and increased ejection fractions from 55.80±9.25 to 72.31±12.15 (P<0.05). Losartan significantly enhanced IL-4, and decreased IFN-γ, TNF-α and IL-17 (all P<0.05). In the in vitro experiment, losartan had no influence on virus titers. SIGNIFICANCE: Losartan protects mice against CVB3-induced CVM, most likely through upregulating Th2 responses, and down-regulating Th1 and Th17 responses.
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