Autophagy as a mechanism for myolysis of cardiomyocytes in mitral regurgitation.
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, 68·4 ± 18·9% of total myocytes showed moderate-to-severe myolysis, while 64·2 ± 15·8% of total myocytes comprised these cells in right atrial myocardium with sinus rhythm. Immunohistochemical study revealed LC3B-positive myocytes in 8·0% of myocytes without myolysis, 11·9% of myocytes with mild myolysis and 49·4% of myocytes with moderate-to-severe myolysis in right atrial myocardium with sinus rhythm (P < 0·0001). Similarly, in the fibrillating right atria, LC3B-positive myocytes were observed in 5·9% of myocytes without myolysis, 12·2% of myocytes with mild myolysis and 50·7% of myocytes with moderate-to-severe myolysis (P < 0·0001). Moreover, in the fibrillating left atria, LC3B-positive myocytes were observed in 4·9% of myocytes without myolysis, 12·6% of myocytes with mild myolysis and 52·0% of myocytes with moderate-to-severe myolysis (P < 0·0001). 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.
Division of Cardiology and Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. chenmien@ms76.hinet.net
Mien-Cheng
MC
Chen
Jen-Ping
JP
Chang
Ya-Hui
YH
Wang
Wen-Hao
WH
Liu
Wan-Chun
WC
Ho
Hsueh-Wen
HW
Chang
D000368:Aged; D020517:Atrial Appendage; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001343:Autophagy / Q000502:physiology*; D004452:Echocardiography; D005260:Female; D006325:Heart Atria; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000502:physiology*; D008944:Mitral Valve Insufficiency / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology*