Molecular and biological changes in the myocardium of male BALB/c mice at different stages of autoimmune myocarditis

Objective: to evaluate morphological and molecular biological changes in the myocardium of male BALB/c mice on days 14, 28, 42, and 60 of experimental autoimmune myocarditis. Materials and Methods. Experimental autoimmune myocarditis was induced in adult male BALB/c mice (n=60) by three subcutaneous immunizations with porcine myocardial homogenate in complete Freund's adjuvant. Animals were sacrificed on days 14, 28, 42, and 60. Morphological examination was performed using hematoxylin and eosin staining, Mallory's trichrome staining, immunohistochemical analysis (CD3, CD68), and real-time quantitative PCR to assess the expression of Hif1a, Nfkb, Il1b, Il6, Il10, and Tgfb genes. Results. On day 14, signs of acute inflammation were detected: lymphohistiocytic infiltration with CD3+ T lymphocytes and increased expression of Hif1a, Nfkb, Il1b, and Tgfb. By day 28, a decrease in pro-inflammatory gene expression and formation of fibrosis foci were observed. On day 42, expression levels of Il6, Il10, Hif1a, and Tgfb increased; morphologically, signs of cardiomyocyte damage were identified. By day 60, high expression of Il6 and Il10 persisted in the presence of myocytolysis. Conclusion. The identified dynamics of molecular biological changes indicate the formation of a chronic inflammatory process with a predominance of anti-inflammatory cytokines IL-6 and IL-10 at late stages of autoimmune myocarditis in male BALB/c mice, which may contribute to disease progression and development of dilated cardiomyopathy.