Back to Search
Start Over
Antiadrenergic autoimmunity in postural tachycardia syndrome.
- Source :
-
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology [Europace] 2017 Jul 01; Vol. 19 (7), pp. 1211-1219. - Publication Year :
- 2017
-
Abstract
- Aims: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR).<br />Methods and Results: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity.<br />Conclusion: These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.<br /> (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Subjects :
- Adolescent
Adrenergic alpha-1 Receptor Agonists pharmacology
Adrenergic beta-1 Receptor Agonists pharmacology
Adrenergic beta-2 Receptor Agonists pharmacology
Adult
Animals
Arterioles drug effects
Arterioles metabolism
CHO Cells
Case-Control Studies
Cricetulus
Dose-Response Relationship, Drug
Female
Humans
In Vitro Techniques
Male
Postural Orthostatic Tachycardia Syndrome blood
Postural Orthostatic Tachycardia Syndrome diagnosis
Rats
Receptors, Adrenergic, alpha-1 drug effects
Receptors, Adrenergic, alpha-1 genetics
Receptors, Adrenergic, alpha-1 metabolism
Receptors, Adrenergic, beta-1 drug effects
Receptors, Adrenergic, beta-1 genetics
Receptors, Adrenergic, beta-1 metabolism
Receptors, Adrenergic, beta-2 drug effects
Receptors, Adrenergic, beta-2 genetics
Receptors, Adrenergic, beta-2 metabolism
Transfection
Vasoconstriction drug effects
Young Adult
Abdominal Muscles blood supply
Autoantibodies blood
Autoimmunity
Immunoglobulin G blood
Postural Orthostatic Tachycardia Syndrome immunology
Receptors, Adrenergic, alpha-1 immunology
Receptors, Adrenergic, beta-1 immunology
Receptors, Adrenergic, beta-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-2092
- Volume :
- 19
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 27702852
- Full Text :
- https://doi.org/10.1093/europace/euw154