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- Title
Vaccine Targeting Alpha 1D-Adrenergic Receptor Improved Metabolic Syndrome in Mice.
- Authors
Li, Xin; Ma, Wenrui; Zhou, Yanzhao; Li, Chang; Shi, Dingyang; Kuang, Wenlong; Wu, Jiacheng; Liao, Yuhua; Qiu, Zhihua; Zhou, Zihua
- Abstract
Purpose: Metabolic syndrome (MetS) is a complex chronic disease that includes obesity and hypertension, with rising evidence demonstrating that sympathetic nervous system (SNS) activation plays a key role. Our team designed a therapeutic vaccine called ADRQβ-004 targeting the α1D-adrenergic receptor (α1D-AR). This study was performed to investigate whether the ADRQβ-004 vaccine improves MetS by modulating SNS activity. Methods: C57BL/6N mice were fed a high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) combination diet for 18 weeks to elicit MetS. The MetS mice were subcutaneously immunized with the ADRQβ-004 vaccine four times to evaluate the therapeutic efficacy in obesity and hypertension and other associated abnormalities related to MetS by conducting echocardiographic, histological, and biochemical analyses. Results: The ADRQβ-004 vaccine induced strong antibody production and maintained a high anti-ADR-004 antibody titer in MetS mice. The ADRQβ-004 vaccine improved obesity (P < 0.001) and decreased systolic blood pressure (P < 0.001). Improvements in dysregulated glucose homeostasis and dyslipidemia resulting from the ADRQβ-004 vaccine were also confirmed. Furthermore, the ADRQβ-004 vaccine attenuated cardiovascular functional (P = 0.015) and structural changes (P < 0.001), decreased fat accumulation (P = 0.012) and inflammation (P = 0.050) in the epididymal white adipose tissue, and alleviated hepatic steatosis (P = 0.043) involved in MetS. Moreover, the ADRQβ-004 vaccine improved systematic and visceral organs SNS activities in the MetS. Conclusion: This study demonstrated for the first time that the ADRQβ-004 vaccine targeting α1D-AR improved obesity, hypertension, dyslipidemia, and dysglycemia, and further reduced end-organ damage, which may provide new motivation for MetS research.
- Subjects
METABOLIC syndrome; WHITE adipose tissue; SYMPATHETIC nervous system; ADIPOSE tissue diseases; HYPERGLYCEMIA; SYSTOLIC blood pressure; ANTIBODY titer
- Publication
Cardiovascular Drugs & Therapy, 2024, Vol 38, Issue 3, p539
- ISSN
0920-3206
- Publication type
Article
- DOI
10.1007/s10557-022-07418-9