Active immunization of combined β1-adrenoceptor and M2-muscarinic receptor peptides induces cardiac hypertrophy in rabbits

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

doi:10.1016/s1071-9164(99)90009-x

Cited by 33 publications

(18 citation statements)

References 29 publications

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“…G protein-coupled receptors comprise a large protein family of transmembrane receptors related to GTP-binding regulatory proteins and include the M2 muscarinic receptor, β1 adrenergic receptor, α1 adrenergic receptor and AT1 receptor [7,9,10,11]. These receptors can sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses, playing critical roles in the regulation of the cardiovascular system [12,13,14].…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Zhao

2014

Cardiology

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Objectives: To explore the relationship between the autoantibodies against the β1 and AT1 receptors and left ventricular dilatation in patients with type 2 diabetes (T2DM). Methods: The autoantibodies against the β1 and angiotensin II type 1 (AT1) receptors of T2DM patients with and without hypertension were screened by ELISA. Multiple logistic regression was used to analyze the risk factors for left ventricular dilatation. The reversing effect of left ventricular dilatation was evaluated after receptor blocker treatment. Results: The positive rates of autoantibodies against the β1 and AT1 receptors (43.0 and 44.1%, respectively) in T2DM patients with hypertension were significantly higher than those in normotensive patients (16.0 and 10.4%, respectively; all p < 0.01). Furthermore, among T2DM patients with hypertension, the positive rates (61.4 and 64.9%, respectively) in patients with left ventricular dilatation were remarkably higher than those with normal left ventricular dimensions (34.4 and 36.1%, respectively; all p < 0.01). The presence of β1 receptor antibody and AT1 receptor antibody were risk factors for left ventricular dilatation (p < 0.05). The curative effect of metoprolol tartrate and valsartan in reversing left ventricular hypertrophy in the group positive for autoantibodies was much better than in the negative group. Conclusion: The findings show that autoantibodies against the β1 and AT1 receptors may play a role in predicting left ventricular dilatation in T2DM patients in combination with hypertension. Metoprolol tartrate and valsartan are effective and safe in the treatment of these patients.

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Section: Discussionmentioning

confidence: 99%

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Zhao

2014

Cardiology

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“…Fu et al discovered that anti-peptide antibodies directed against the M2 human muscarinic acetylcholine receptor had agonist-like activity on the myocardium. Further studies by Fu et al in experimental models indicated that anti M2 receptor antibodies could inhibit beta-adrenoceptor mediated inotropic response in myocardium and induce myocardial damage as well as hypertrophic or dilated cardiomyopathies [19,20] . Similarly, anti-beta-1 adrenoceptor antibodies also stimulated beta receptor and induced cardiomyopathy [21,22] .…”

Section: Discussionmentioning

confidence: 99%

Throat infection, neck and chest pain and cardiac response: A persistent infection-related clinical syndrome

Zhou

Yan

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Dizziness, chest discomfort, chest depression and dyspnea are a group of symptoms that are common complaints in clinical practice. Patients with these symptoms are usually informed that while neurosis consequent to coronary heart disease is excluded nonetheless they remain unhealthy with no rational explanation or treatment. 165 cases of these symptoms and 85 control subjects were reviewed and underwent further medical history inquiry, routine EKG test and cardiac ultrasound examination. Thirty-five patients received coronary artery angiography to exclude coronary heart disease. Serum myocardial autoantibodies against beta(1)-adrenoceptor, alpha-myosin heavy chain, M(2)-muscarinic receptor and adenine-nucleotide translocator were tested, and inflammatory cytokines and high sensitivity C-reaction protein were measured and lymphocyte subclass was assayed by flow cytometry. All patients had a complex of four symptoms or tetralogy: (1) persistent throat or upper respiratory tract infection, (2) neck pain, (3) chest pain and (4) chest depression or dyspnea, some of them with anxiety. Anti-myocardial autoantibodies (AMCAs) were present in all patients vs. 8% in controls. TNF-alpha, IL-1 and IL-6 were significantly higher in patients than in controls (P<0.01). CD3(+) and CD4-CD8(+) lymphocytes were significantly higher and CD56(+) lymphocytes lower in patients than those in controls (P<0.01). The ratio of serum pathogen antibodies positive against Coxsackie virus-B, cytomegalovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae were all markedly higher in patients. These data led to identification of a persistent respiratory infection-related clinical syndrome, including persistent throat infection, neck spinal lesion, rib cartilage inflammation, symptoms of cardiac depression and dyspnea with or without anxiety.

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“…Similarly, chronic adrenergic stimulation mediated by antibodies may have a cardiotoxic effect resembling that caused by catecholamines, which induce cardiac changes similar to those observed in Chagas' disease, namely induction of microfocal lesions associated with a mononuclear cell infiltrate with increased involvement of the left ventricle, and particularly the left ventricular apex [35]. Indeed, an immunological response against β1‐AR provoked by immunization with peptides derived from the second extracellular loop of this receptor caused structural damage to myocardial cells and tissue [36,37]. Jahns et al .…”

Section: Discussionmentioning

confidence: 99%

Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease

Labovsky

Smulski

Gómez

et al. 2007

Clinical and Experimental Immunology

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SummaryChronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against the C-terminal region of the ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with the second extracellular loop of b1-adrenergic receptor (b1-AR, peptide H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human b1-AR, the aim of this study was to investigate further the physical interaction between cChHD IgGs and the human b1-AR. Immunofluorescence assays demonstrated the binding of these antibodies to the receptor expressed on stably transfected cells, together with a b1-AR agonist-like effect. In addition, immunoadsorption of the serum samples from cChHD patients with a commercially available matrix, containing peptides representing the first and the second extracellular loop of the b1-AR, completely abolished reactivity against the H26R peptide and the physiological response to the receptor. The follow-up of this specificity after in vitro immunoadsorption procedures suggests that this treatment might be used to diminish significantly the serum levels of anti-b1-AR antibodies in patients with Chagas heart disease.

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Active immunization of combined β1-adrenoceptor and M2-muscarinic receptor peptides induces cardiac hypertrophy in rabbits

Cited by 33 publications

References 29 publications

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation

Throat infection, neck and chest pain and cardiac response: A persistent infection-related clinical syndrome

Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease

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