Transfer of Rabbit Autoimmune Cardiomyopathy into Severe Combined Immunodeficiency Mice

Matsui, Shinobu; Fu, Michael; Hayase, Mituru; Katsuda, Shogo; Yamaguchi, Nobuo; Teraoka, Kohei; Kurihara, Takayuki; Takekoshi, Noboru

doi:10.1097/00005344-200312001-00021

Cited by 23 publications

(11 citation statements)

References 25 publications

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“…19 -22 AA␤ARs have been induced in experimental animal models, are associated with the onset of cardiomyopathy, and have been passively transferred from either a human source or from animal models to produce a cardiomyopathy. [22][23][24] These characteristics fulfill the postulates of Witebsky et al 25 for proof of an autoimmune cardiomyopathy. A most difficult corollary is to remove the antibody and thereby demonstrate improvement and/or cure of the disease.…”

Section: Discussionsupporting

confidence: 60%

Autoimmune Hypertensive Syndrome

Kem

Yu²,

Patterson³

et al. 2007

Hypertension

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Section: Discussionsupporting

confidence: 60%

Autoimmune Hypertensive Syndrome

Kem

Yu²,

Patterson³

et al. 2007

Hypertension

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“…Moreover, after 6 months of immunization the rabbits were found to develop LV-hypertrophy rather than LV-dilatation (as determined by echocardiography and histology) which was, however, no longer present after 12 months of immunization, perhaps indicating the transition into an early DCM-phenotype [40]. In the following time, (indirect) evidence for a pathogenic role of anti-β 1 -EC II has been supported further by the fact that intraperitoneal injection of blood lymphocytes either from immunized anti-β 1 -EC II -positive rabbits [50], or from anti-β 1 -AR-positive DCM patients [51] into immunodeficient mice -in order to avoid the expected immune reaction against rabbit or human non-self proteins -may lead to an early stage of cardiac dilatation. Nonetheless, direct evidence for a cause-andeffect relation between anti-β 1 -AR antibodies and DCM still remained to be established.…”

Section: Stimulatory Anti-β 1 -Ecii (Auto-)antibodies Are Pathogenicmentioning

confidence: 98%

Beta 1-adrenergic receptor-directed autoimmunity as a cause of dilated cardiomyopathy in rats

Jahns

Boivin

Lohse

2006

International Journal of Cardiology

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“…The severe combined immunodeficiency mouse has been used to demonstrate a pathogenic role of peripheral blood leukocytes from patients with myocarditis (14) and dilated cardiomyopathy (15). Transfer of IgG and/or peripheral blood lymphocytes from rabbit autoimmune cardiomyopathy to severe combined deficiency mice has been shown to increase heart weight, blood brain natriuretic peptide and focal infiltration of inflammatory cells in the myocardium (16).…”

Section: Introductionmentioning

confidence: 99%

Adoptive passive transfer of rabbit β1-adrenoceptor peptide immune cardiomyopathy into the Rag2−/− mouse: Participation of the ER stress

Mao

Iwai

Fukuoka

et al. 2008

Journal of Molecular and Cellular Cardiology

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Auto-antibodies against the β 1 -adrenoceptors are present in 30−40% of patients with dilated cardiomyopathy. Recently, a synthetic peptide corresponding to a sequence of the second extracellular loop of the human β 1 -adrenoceptor (β 1 -EC II ) has been shown to produce endoplasmic reticulum (ER) stress, myocyte apoptosis and cardiomyopathy in immunized rabbits. To study the direct cardiac effects of anti-β 1 -EC II antibody in intact animals and if they are mediated via β 1 -adrenoceptor stimulation, we administered IgG purified from β 1 -EC II -immunized rabbits to recombination activating gene 2 knock-out (Rag2 −/− ) mice every two weeks with and without metoprolol treatment. Serial echocardiography and cardiac catheterization showed that β 1 -EC II IgG reduced cardiac systolic function after 3 months. This was associated with increase in heart weight, myocyte apoptosis, activation of caspase-3, -9 and -12, and increased ER stress as evidenced by upregulation of GRP78 and CHOP and cleavage of ATF6. The Rag2 −/− mice also exhibited increased phosphorylation of CaMKII and p38 MAPK. Metoprolol administration, which attenuated the phosphorylation of CaMKII and p38 MAPK, reduced the ER stress, caspase activation and cell death. Finally, we employed the small-interfering RNA technology to reduce caspase-12 in cultured rat cardiomyocytes. This reduced not only the increase of cleaved caspase-12 but also of the number of myocyte apoptosis produced by β 1 -EC II IgG. Thus, we conclude that ER stress plays an important role in cell death and cardiac dysfunction in β 1 -EC II IgG cardiomyopathy, and the effects of β 1 -EC II IgG are mediated via the β 1 -adrenergic receptor.

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Transfer of Rabbit Autoimmune Cardiomyopathy into Severe Combined Immunodeficiency Mice

Cited by 23 publications

References 25 publications

Autoimmune Hypertensive Syndrome

Autoimmune Hypertensive Syndrome

Beta 1-adrenergic receptor-directed autoimmunity as a cause of dilated cardiomyopathy in rats

Adoptive passive transfer of rabbit β1-adrenoceptor peptide immune cardiomyopathy into the Rag2−/− mouse: Participation of the ER stress

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