Regulation of the Heme Oxygenase-1/carbon monoxide system by hydrogen sulfide in murine coxsackievirus B3-induced myocarditis

Abstract

To explore the impact of hydrogen sulfide (H2S) on the heme oxygenase-1 (HO-1)/carbon monoxide (CO) system in coxsackie virus B3 (CVB3)-induced myocarditis. A total of 80 Balb/c mice were divided randomly into four groups designated N, C, P and S. Group N served as the negative control while groups C, P, and S were infected with CVB3 to induce myocarditis. Group P was additionally treated with DL-propargylglycine (PAG) to inhibit the generation of H2S while Group S was treated with NaHS, an H2S donor. Ten days after infection, heart sections were scored for histopathology. We also measured carboxyhemoglobin (COHb) levels in the blood and HO-1 expression by immunohistochemistry. 1. Each CVB3-infected group (C, P, and S) exhibited increased pathology, COHb levels, and HO-1 expression compared to uninfected controls. 2. Regarding histopathology, the score of group P was worse, while that of group S was better, than that of group C. 3. The P group COHb level was lower than group C, while the S group COHb level was higher than group C. 4. Positive HO-1 expression was seen in group C with reduced expression in group P and increased expression in group S. 5. A positive correlation was observed between the COHb concentration and HO-1expression; alternatively, a negative correlation was found between the histopathologic scores and both the concentration of COHb and the expression level of HO-1. Modulation of H2S can play a regulatory role in the pathogenesis of VMC by impacting the HO-1/CO pathway.