Elevated expression of PDGF-C in coxsackievirus B3-induced chronic myocarditis

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Abstract
Aims Coxsackievirus B3 (CVB3) is a frequent cause of human chronic myocarditis and subsequent fibrosis, leading to dilated cardiomyopathy. The molecular processes underlying the development of fibrosis are poorly understood. Enhanced levels of platelet-derived growth factors (PDGFs), especially PDGF-C, have recently been linked with the development of different forms of fibrosis. Therefore, the expression of PDGF was analysed in hearts of CVB3-infected major histocompatability complex class II knockout mice. The latter were recently established as mouse model mimicking the chronic inflammation and fibrosis characteristic for this disease. Methods and results Expression of PDGF was analysed by reverse transcription–polymerase chain reaction, in situ hybridization, and immunohistochemistry. Hearts of C57BL/6 mice served as controls because infection of these animals leads to acute cardiac inflammation, but the hearts heal without signs of chronic inflammation. In uninfected hearts, basal expression of PDGF, notably PDGF-C, was detectable throughout the heart. The chronic inflammatory process was associated with elevated and sustained expression of all tested PDGF isoforms. Immunostaining and in situ hybridization analysis localized enhanced PDGF levels to areas with highest virus load and inflammatory infiltrations, adjacent to fibrotic areas. Conclusion PDGF may participate in fibrosis development in CVB3-induced myocarditis. Therefore, PDGF signalling may be considered a target for therapeutic interference.