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Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice.

Authors: Okazaki, T  Tanaka, Y  Nishio, R  Mitsuiye, T  Mizoguchi, A  Wang, J  Ishida, M  Hiai, H  Matsumori, A  Minato, N  Honjo, T 
Citation: Okazaki T, etal., Nat Med. 2003 Dec;9(12):1477-83. Epub 2003 Nov 2.
Pubmed: (View Article at PubMed) PMID:14595408
DOI: Full-text: DOI:10.1038/nm955

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.


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CRRD Object Information
CRRD ID: 9589058
Created: 2014-11-05
Species: All species
Last Modified: 2014-11-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.