Induction of cardiomyocyte apoptosis by anti-cardiac myosin heavy chain antibodies in patients with acute myocardial infarction.
Autoimmune is involved in the pathogenesis of ventricular remodeling in acute myocardial infarction (AMI). In the present study, we investigated the effect of anti-cardiac myosin heavy chain antibodies (AMHCA) from patients with AMI on rat cardiomyocyte apoptosis. Cardiomyocyte apoptosis was observed and measured by DNA end labeling and Annexin-V/PI double-staining assay. The expression of apoptosis related p53 and Bcl-2 protein and the second messenger calcium were detected respectively by Western blotting, patch clamp and confocal calcium imaging. The results showed that AMHCA was able to induce cardiomyocyte apoptosis in a dose dependent manner. Apoptosis-accelerating nucleoprotein p53 was up-regulated, while apoptosis-inhibiting cytoplasmic protein Bcl-2 was down-regulated. In parallel, cytoplasmic calcium concentration was elevated. There was no effect on L-type calcium currents. It is concluded that AMHCA in patients with AMI as a novel triggering factor can induce cardiomyocyte apoptosis, which contributes to ventricular remodeling.
Department of Cardiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. liukun0329@163.com
Kun
K
Liu
Liang
L
Shao
Li
L
Wang
Yanping
Y
Ding
Guanhua
G
Su
Jue
J
Wang
Yuhua
Y
Liao
Zhaohui
Z
Wang
D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000276:immunology*; D051381:Rats; D020257:Ventricular Remodeling
D001323:Autoantibodies; D018995:Myosin Heavy Chains