A novel vaccine targeting β1-adrenergic receptor

被引:8
|
作者
Ke, Fan [1 ,2 ,3 ]
Kuang, Wenlong [1 ,2 ,3 ]
Hu, Xiajun [1 ,2 ,3 ]
Li, Chang [1 ,2 ,3 ]
Ma, Wenrui [1 ,2 ,3 ]
Shi, Dingyang [1 ,2 ,3 ]
Li, Xin [1 ,2 ,3 ]
Wu, Zhijie [1 ,2 ,3 ]
Zhou, Yanzhao [1 ,2 ,3 ]
Liao, Yuhua [1 ,2 ,3 ]
Qiu, Zhihua [1 ,2 ,3 ]
Zhou, Zihua [1 ,2 ,3 ]
机构
[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiol, Wuhan 430022, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Hubei Key Lab Biol Targeted Therapy, Wuhan 430022, Peoples R China
[3] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Hubei Prov Engn Res Ctr Immunol Diag & Therapy Car, Wuhan 430022, Peoples R China
基金
中国国家自然科学基金;
关键词
beta; 1-AR; Cardiac Remodeling; Hypertension; Heart Failure; Therapeutic Vaccine; BETA-ADRENERGIC-RECEPTOR; HEART-FAILURE; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; BETA(1)-ADRENERGIC RECEPTORS; NERVOUS-SYSTEM; TSH RECEPTOR; SUDDEN-DEATH; AUTOANTIBODIES; ANTIBODIES;
D O I
10.1038/s41440-023-01265-3
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Beta-blockers are widely used in the treatment of hypertension, heart failure and ischemic heart disease. However, unstandardized medication results in diverse clinical outcomes in patients. The main causes are unattained optimal doses, insufficient follow-up and patients' poor adherence. To improve the medication inadequacy, our team developed a novel therapeutic vaccine targeting ss 1-adrenergic receptor (ss 1-AR). The ss 1-AR vaccine named ABRQ ss-006 was prepared by chemical conjugation of a screened ss 1-AR peptide with Q ss virus like particle (VLP). The antihypertensive, anti-remodeling and cardio-protective effects of ss 1-AR vaccine were evaluated in different animal models. The ABRQ ss-006 vaccine was immunogenic that induced high titers of antibodies against ss 1-AR epitope peptide. In the NG-nitro-L-arginine methyl ester (L-NAME) + Sprague Dawley (SD) hypertension model, ABRQ ss-006 lowered systolic blood pressure about 10 mmHg and attenuated vascular remodeling, myocardial hypertrophy and perivascular fibrosis. In the pressure-overload transverse aortic constriction (TAC) model, ABRQ ss-006 significantly improved cardiac function, decreased myocardial hypertrophy, perivascular fibrosis and vascular remodeling. In the myocardial infarction (MI) model, ABRQ ss-006 effectively improved cardiac remodeling, reduced cardiac fibrosis and inflammatory infiltration, which was superior to metoprolol. Moreover, no significant immune-mediated damage was observed in immunized animals. The ABRQ ss-006 vaccine targeting ss 1-AR showed the effects on hypertension and heart rate control, myocardial remodeling inhibition and cardiac function protection. These effects could be differentiated in different types of diseases with diverse pathogenesis. ABRQ ss-006 could be a novel and promising method for the treatment of hypertension and heart failure with different etiologies.
引用
收藏
页码:1582 / 1595
页数:14
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