351. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice.
- Author
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Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, Ishida M, Hiai H, Matsumori A, Minato N, and Honjo T
- Subjects
- Animals, Antibodies, Monoclonal administration & dosage, Antigens, CD, Antigens, Surface genetics, Apoptosis Regulatory Proteins, Base Sequence, Calcium Signaling, Cardiomyopathy, Dilated genetics, Cardiomyopathy, Dilated metabolism, DNA, Complementary genetics, Humans, Mice, Mice, Inbred A, Mice, Inbred BALB C, Mice, Knockout, Mice, Nude, Myocytes, Cardiac immunology, Myocytes, Cardiac metabolism, Programmed Cell Death 1 Receptor, Rats, Rats, Wistar, Antigens, Surface immunology, Autoantibodies metabolism, Cardiomyopathy, Dilated etiology, Cardiomyopathy, Dilated immunology, Troponin I immunology
- Abstract
We recently reported that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against a heart-specific, 30-kDa protein. In this study, we purified the 30-kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal antibodies to cTnI induced dilatation and dysfunction of hearts in wild-type mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and augmented the voltage-dependent L-type Ca2+ current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes.
- Published
- 2003
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