| First Author | Okazaki T | Year | 2003 |
| Journal | Nat Med | Volume | 9 |
| Issue | 12 | Pages | 1477-83 |
| PubMed ID | 14595408 | Mgi Jnum | J:86800 |
| Mgi Id | MGI:2682112 | Doi | 10.1038/nm955 |
| Citation | Okazaki T, et al. (2003) Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med 9(12):1477-83 |
| abstractText | 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 Ca(2+) current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca(2+) influx in cardiomyocytes. |
