Long-term active immunization with a synthetic peptide corresponding to the second extracellular loop of β1-adrenoceptor induces both morphological and functional cardiomyopathic changes in rats.
BACKGROUND
β1-adrenoceptors (β1-ARs) are the predominant receptors in regulating heart functions. β1-ARs contain 7-transmembrane domains (7TM), 3 extracellular loops and 3 intracellular loops. Among these loops, the second extracellular loop of β1-AR (β1-AR-ECII) plays an important role in the pathogenesis of heart failure.


METHODS
(1) Select the sera-negative rats for antibodies against β1-AR-ECII. (2) Detect the level of antibodies against β1-AR-ECII in the process of active immunization with artificial synthetic peptides according to the sequence of human β1-AR-ECII. (3) Observe its long-term role on cardiac structure and function in vivo by immunizing rats. (4) Detect the changes of T lymphocytes subsets in the process of active immunization.


RESULTS
The peptides induced the production of specific autoantibody against β1-AR-ECII. Furthermore, immunization with β1-AR-ECII peptide induced both morphological and functional alterations in the hearts of rats, which potentially results in heart failure. In addition, induction of the autoantibodies against β1-AR-ECII increased the CD4+/CD8+ ratio in the peripheral blood of rats.


CONCLUSIONS
In this study, we determined the effect of anti-β1-AR-ECII autoantibody on morphological and functional cardiomyopathic alterations by immunization of rats with a synthetic peptide corresponding to the β1-AR-ECII for 18 months. These results provide further evidence that autoantibody against β1-AR-ECII is involved in the pathogenesis of heart failure. But the underlying mechanisms need further study.
Zuo
Lin
L
Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
Bao
Haijun
H
Tian
Jue
J
Wang
Xiaoliang
X
Zhang
Suli
S
He
Zhongmei
Z
Yan
Li
L
Zhao
Rongrui
R
Ma
Xin L
XL
Liu
Huirong
H
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D009202:Cardiomyopathies / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005110:Extracellular Space; D006333:Heart Failure / Q000276:immunology* / Q000473:pathology; D006334:Heart Function Tests; D006801:Humans; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D009929:Organ Size / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014611:Vaccination / Q000379:methods*
D001323:Autoantibodies; D010446:Peptide Fragments; D018342:Receptors, Adrenergic, beta-1