P1179 Beta-1-adrenoceptor antibodies induce apoptosis in adult isolated cardiomyocytes

Staudt, Yvonne

doi:10.1016/s0195-668x(03)94471-x

Cited by 3 publications

(6 citation statements)

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“…6,21 Additionally b 1 -AABs are able to induce a dose-dependent increase in cardiomyocyte apoptosis. 22 Whereas b 1 -AABs were usually detectable in ,10% (more often ≤1%) of healthy controls and only in 10-13% of patients with ischaemic cardiomyopathy, 26 -80% of idiopathic DCM patients tested positive for b 1 -AABs. 5,6,10,16,17,23 The large differences in prevalence of b 1 -AABs found in DCM patients are probably in part due to differences in screening strategies.…”

Section: Discussionmentioning

confidence: 98%

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Long‐term benefits of immunoadsorption in β₁‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Dandel

Wallukat

Englert

et al. 2012

European J of Heart Fail

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AimsProlongation of waiting times for heart transplantation (HTx) increases the need for new therapies. In short-term follow-up studies, immunoadsorption (IA) appeared beneficial in dilated cardiomyopathy (DCM) associated with b 1 -adrenoreceptor-autoantibodies (b 1 -AABs). This study aimed to investigate the long-term benefits of IA in HTx candidates with DCM, patients' responsiveness to IA, and the impact of b 1 -AAB removal on IA results. Methods and resultsIn a single-centre retrospective study of prospectively gathered information we evaluated all b 1 -AAB-positive and -negative HTx candidates with end-stage DCM [left ventricular ejection fraction (LVEF) ,30%] who underwent IA between 1995 and 2005 (follow-up thereafter: 5.3 -14.7 years). As controls we used all b 1 -AAB-positive DCM patients referred for HTx during the same time period who received no IA therapy. We also looked for differences in efficacy between unspecific IA (unselective antibody removal) and specific IA (selective b 1 -AAB removal). The main outcome measures were cardiac function and HTx/ventricular assist device (VAD)-free patient survival. The probability for 5-year HTx/VAD-free survival for the108 b 1 -AAB-positive DCM patients who underwent unspecific IA reached 69.4 + 4.4% and was significantly higher (P , 0.05) than for both b 1 -AAB-positive DCM patients without IA (25.4 + 11.4%) and b 1 -AAB-negative DCM patients who also underwent IA (47.4 + 11.5). In patients with high b 1 -AAB levels, unspecific and specific IA showed the same high efficiency in b 1 -AAB removal. LVEF and New York Heart Assocation class improved (P , 0.01) after both, but without differences in improvement after specific or unspecific IA. The prevalence of responders to specific and unspecific IA was similar (78.3% vs. 79.6%). In 76% of the patients with b 1 -AAB reappearance, redetection of AABs coincided with worsening of cardiac function. ConclusionsRemoval of b 1 -AABs by specific or unspecific IA can improve cardiac function allowing long-term stability in endstage DCM, which can spare many patients from HTx or will delay HTx listing for years. In b 1 -AAB-positive DCM patients the benefits of IA appeared to be associated with the removal of these antibodies.--

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Section: Discussionmentioning

confidence: 98%

“…Down‐regulation and excessive β 1 ‐AR desensitization plus alterations in intracellular Ca 2+ handling finally induce cardiomyocyte contractile dysfunction ,. Additionally β 1 ‐AABs are able to induce a dose‐dependent increase in cardiomyocyte apoptosis …”

Section: Discussionmentioning

confidence: 99%

Long‐term benefits of immunoadsorption in β₁‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Dandel

Wallukat

Englert

et al. 2012

European J of Heart Fail

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“…However, because ␣-myosin is sequestered within myocardial cells and is not expressed within the plasma membrane it remained unclear how ␣-myosin AABs can induce cardiomyocyte damage (Lappé et al 2008). A possible mechanism might be the activation of ␤ 1 -adrenoreceptors (␤ 1 -ARs) by anti-␣-myosin AABs because these antibodies can cross-react with the surface ␤ 1 -ARs and antibody mediated activation of ␤ 1 -ARs is known to induce cardiomyocyte apoptosis (Lappé et al 2008;Li et al 2006;Staudt et al 2003).…”

Section: Role Of Autoimmune Mechanismsmentioning

confidence: 99%

“…Chronic ␤ 1 -AR hyperstimulation causes cardiomyocite toxicity mainly due to an intracellular Ca 2+ overload and a reduction of ␤ 1 -AR expression detectable already after 72 h (Wallukat et al 1995. Additionally ␤ 1 -AABs are able to induce a dose-dependent increase in the rate of cardiomyocyte apoptosis (Christ et al 2001;Staudt et al 2003).…”

Section: Autoantibody Interaction With the ˇ1-1 Armentioning

confidence: 99%

Role of β1-adrenoceptor autoantibodies in the pathogenesis of dilated cardiomyopathy

Dandel¹,

Wallukat²,

Potapov³

et al. 2012

Immunobiology

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“…Currently, the pathogenic effect is blamed on inappropriate ino‐ and chronotropism leading to down‐regulation and desentization of the cardiac β 1 ‐adrenoceptor (Jahns et al ., 2004; 2006a). However, it has also been shown that such autoantibodies stimulate apoptosis (Staudt et al ., 2003; Jane‐wit et al ., 2007) and stress responses of the endoplasmic reticulum (Liu et al ., 2008) in isolated cardiomyocytes, suggesting that the pathogenic mechanism may also involve direct myocardial cytotoxicity. The high incidence of stimulatory β 1 ‐adrenoceptor autoantibodies in DCM (Magnusson et al ., 1994; Jahns et al ., 1999b; Staudt et al ., 2001; Nikolaev et al ., 2007) and Chagas' disease (Labovsky et al ., 2007) and the predictive value of β 1 ‐adrenoceptor autoantibodies for the development of Chagas' cardiomyopathy (Wallukat et al ., 2010) supports the hypothesis that these autoantibodies can trigger chronic left ventricular dysfunction not only in immunized rodents but also in human patients (Jahns et al ., 2006b).…”

Section: Evidence That Stimulatory β1‐adrenoceptor Autoantibodies Caumentioning

confidence: 99%

Drug‐like actions of autoantibodies against receptors of the autonomous nervous system and their impact on human heart function

Herda

Felix

Boege

2012

British J Pharmacology

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Antibodies against cholinergic and adrenergic receptors (adrenoceptors) are frequent in serum of patients with chronic heart failure. Their prevalence is associated with Chagas' disease, idiopathic dilated cardiomyopathy (DCM), and ischaemic heart disease. Among the epitopes targeted are first and second extracellular loops of the β-adrenergic (β-adrenoceptor) and M2 muscarinic receptor. β1-adrenoceptor autoantibodies affect radioligand binding and cardiomyocyte function similar to agonists. Corresponding rodent immunizations induce symptoms compatible with chronic heart failure that are reversible upon removal of the antibodies, transferable via the serum and abrogated by adrenergic antagonists. In DCM patients, prevalence and stimulatory efficacy of β1-adrenoceptor autoantibodies are correlated to the decline in cardiac function, ventricular arrhythmia and higher incidence of cardiac death. In conclusion, such autoantibodies seem to cause or promote chronic human left ventricular dysfunction by acting on their receptor targets in a drug-like fashion. However, the pharmacology of this interaction is poorly understood. It is unclear how the autoantibodies trigger changes in receptor activity and second messenger coupling and how that is related to the pathogenesis and severity of the associated diseases. Here, we summarize the available evidence regarding these issues and discuss these findings in the light of recent knowledge about the conformational activation of the human β2-adrenoceptor and the properties of bona fide cardiopathogenic autoantibodies derived from immune-adsorption therapy of DCM patients. These considerations might contribute to the conception of therapy regimen aimed at counteracting or neutralizing cardiopathogenic receptor autoantibodies.

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P1179 Beta-1-adrenoceptor antibodies induce apoptosis in adult isolated cardiomyocytes

Cited by 3 publications

References 0 publications

Long‐term benefits of immunoadsorption in β₁‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Long‐term benefits of immunoadsorption in β₁‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Role of β1-adrenoceptor autoantibodies in the pathogenesis of dilated cardiomyopathy

Drug‐like actions of autoantibodies against receptors of the autonomous nervous system and their impact on human heart function

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P1179 Beta-1-adrenoceptor antibodies induce apoptosis in adult isolated cardiomyocytes

Cited by 3 publications

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Long‐term benefits of immunoadsorption in β1‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Long‐term benefits of immunoadsorption in β1‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Role of β1-adrenoceptor autoantibodies in the pathogenesis of dilated cardiomyopathy

Drug‐like actions of autoantibodies against receptors of the autonomous nervous system and their impact on human heart function

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Product

Resources

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Long‐term benefits of immunoadsorption in β₁‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Long‐term benefits of immunoadsorption in β₁‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy