Autophagy as a mechanism for myolysis of cardiomyocytes in mitral regurgitation

P>Background Myolysis of atrial cardiomyocytes occurs in patients with severe mitral and tricuspid regurgitation. This morphological remodelling may involve autophagy. Methods This study comprised 20 patients (10 with long-standing persistent atrial fibrillation and 10 with sinus rhythm) with severe mitral and tricuspid regurgitation. Atrial appendageal tissues were obtained during surgery. The appearance of autophagosomes (LC3B) in myocytes can reflect autophagy induction. Complement 9 is used as a reliable marker of oncosis. Results In the fibrillating right atria, 68 center dot 4 +/- 18 center dot 9% of total myocytes showed moderate-to-severe myolysis, while 64 center dot 2 +/- 15 center dot 8% of total myocytes comprised these cells in right atrial myocardium with sinus rhythm. Immunohistochemical study revealed LC3B-positive myocytes in 8 center dot 0% of myocytes without myolysis, 11 center dot 9% of myocytes with mild myolysis and 49 center dot 4% of myocytes with moderate-to-severe myolysis in right atrial myocardium with sinus rhythm (P < 0 center dot 0001). Similarly, in the fibrillating right atria, LC3B-positive myocytes were observed in 5 center dot 9% of myocytes without myolysis, 12 center dot 2% of myocytes with mild myolysis and 50 center dot 7% of myocytes with moderate-to-severe myolysis (P < 0 center dot 0001). Moreover, in the fibrillating left atria, LC3B-positive myocytes were observed in 4 center dot 9% of myocytes without myolysis, 12 center dot 6% of myocytes with mild myolysis and 52 center dot 0% of myocytes with moderate-to-severe myolysis (P < 0 center dot 0001). None of the atrial myocytes displayed intracellular deposition of complement 9. Conclusions Induction of autophagy, but not oncosis, occurs in most cases of atrial cardiomyocytes with severe mitral and tricuspid regurgitation, even those without atrial fibrillation, and is closely associated with the development of myolysis in this disease.