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

被引：567

作者：

Okazaki, T

Tanaka, Y

Nishio, R

Mitsuiye, T

Mizoguchi, A

Wang, J

Ishida, M

Hiai, H

Matsumori, A

Minato, N

Honjo, T ^{[1
]}

机构：

[1] Kyoto Univ, Dept Med Chem & Mol Biol, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan

[2] Kyoto Univ, Dept Immunol & Cell Biol, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068501, Japan

[3] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan

[4] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Sakyo Ku, Kyoto 6068501, Japan

[5] Kyoto Univ Hosp, Div Emergency Med, Sakyo Ku, Kyoto 6068507, Japan

[6] Kyoto Univ, Grad Sch Med, Dept Physiol & Biophys, Sakyo Ku, Kyoto 6068501, Japan

[7] Mie Univ, Dept Anat, Grad Sch Med, Tsu, Mie 5148507, Japan

[8] Kyoto Univ, Dept Pathol & Biol Dis, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan

来源：

NATURE MEDICINE | 2003年 / 9卷 / 12期

关键词：

D O I：

10.1038/nm955

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Ca2+ influx in cardiomyocytes.

引用

页码：1477 / 1483

页数：7

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[11] ESDN, a novel neuropilin-like membrane protein cloned from vascular cells with the longest secretory signal sequence among eukaryotes, is up-regulated after vascular injury [J].