Back to Search
Start Over
Antiadrenergic autoimmunity in postural tachycardia syndrome
- Source :
- Europace
- Publication Year :
- 2016
- Publisher :
- Oxford University Press (OUP), 2016.
-
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). 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. 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.
- Subjects :
- Male
DISORDER
Cardiac & Cardiovascular Systems
Allosteric activation
Adrenergic
Autoimmunity
030204 cardiovascular system & hematology
Immunoglobulin G
0302 clinical medicine
HYPOTENSION
Medicine
Adrenergic receptors
Abdominal Muscles
biology
Pathophysiology
3. Good health
Arterioles
Adrenergic beta-1 Receptor Agonists
Female
Cardiology and Cardiovascular Medicine
Life Sciences & Biomedicine
INAPPROPRIATE SINUS TACHYCARDIA
medicine.drug
Adult
ORTHOSTATIC INTOLERANCE
medicine.medical_specialty
Adolescent
CONSENSUS STATEMENT
CHO Cells
In Vitro Techniques
Transfection
DIAGNOSIS
Syncope
Contractility
Postural Orthostatic Tachycardia Syndrome
Young Adult
03 medical and health sciences
Cricetulus
Clinical Research
Vasovagal syncope
Receptors, Adrenergic, alpha-1
Physiology (medical)
Internal medicine
Heart rate
MANAGEMENT
Animals
Humans
Adrenergic beta-2 Receptor Agonists
Phenylephrine
Autoantibodies
Science & Technology
Dose-Response Relationship, Drug
Postural tachycardia syndrome
business.industry
1103 Clinical Sciences
medicine.disease
Inappropriate sinus tachycardia
Rats
NITROGLYCERIN
Editor's Choice
Endocrinology
Cardiovascular System & Hematology
Vasoconstriction
Case-Control Studies
Cardiovascular System & Cardiology
biology.protein
Adrenergic alpha-1 Receptor Agonists
Receptors, Adrenergic, beta-2
Receptors, Adrenergic, beta-1
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15322092 and 10995129
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- EP Europace
- Accession number :
- edsair.doi.dedup.....fa88058e04a6b7043a3a6d878717206f