Relationship between autoantibody to the angiotensin II-1 receptor and cardiovascular manifestations of Graves' disease.
OBJECTIVE
To investigate the role of autoantibody against angiotensin II-1 receptor (AT1-AA) in patients with cardiovascular manifestations of Graves' disease (GD).


METHODS
The epitope of the second extracellular loop of AT1 receptor (165-191) was synthesized and used as antigens to screen the autoantibody by enzyme linked immunosorbent assay (ELISA). The patients with GD were divided into the patients with cardiovascular manifestations associated to GD (Group A, n=58) and the patients with GD not complicated by heart disease (Group B, n=60). 40 healthy subjects were included in the study (Group C, n=40). Echocardiography was performed and the differences of echocardiography parameters were compared between AT1-AA positive and negative groups in group A. Factors related to left heart enlargement were analyzed by multiple logistic regression.


RESULTS
(1) The frequency of AT1-AA in Group A (52.2%, 32/58) were significantly higher than those in Group B (16.7%, 10/60) and Group C (12.5%, 5/40) (all p<0.001). (2) There were no differences in the level of TGAb, TPOAb and TRAb between AT1-AA positive and negative groups in patients with GD (all p>0.05). (3) In patients with cardiovascular manifestations of GD, the ratios between left atrial and ventricular enlargement (LAE and LVE) were significantly higher in the AT1-AA positive group than in the AT1-AA negative group (68.8% vs. 26.9%, 62.5% vs. 23.1%, all p<0.01); the frequency of atrial fibrillation differed significantly between these 2 groups (53.1% vs. 19.2%, p<0.01). (4) Regression analysis demonstrated that the positive AT1-AA and course of GD were significantly correlated to the presence of LAE and LVE.


CONCLUSIONS
AT1-AA plays an important role in the pathogenesis of cardiovascular manifestations associated to GD. Especially, AT1-AA is involved in left cardiac dilatation of GD complicated by heart disease, which represents a cardio-vascular risk factor for GD patients.
Wuhan Clinical Medicine College, Southern Medical University, Wuhan, China.
J
J
Xu
Department of Endocrinology and metabolism, Wuhan General Hospital of Guangzhou Command, Wuhan, China.
L
L
Zhao
Department of Endocrinology and metabolism, Wuhan General Hospital of Guangzhou Command, Wuhan, China.
G
G
Xiang
Department of Endocrinology and metabolism, Wuhan General Hospital of Guangzhou Command, Wuhan, China.
C
C
Xu
D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000276:immunology*; D004452:Echocardiography; D000939:Epitopes / Q000276:immunology; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011945:Receptors, Angiotensin / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D011945:Receptors, Angiotensin; C006606:anti-thyroglobulin