ATRQβ‐001 Vaccine Prevents Experimental Abdominal Aortic Aneurysms

Abstract

BackgroundWe have developed a peptide vaccine named ATRQβ‐001, which was proved to retard signal transduction initiated by angiotensin II (Ang II). Ang II was implicated in abdominal aortic aneurysm (AAA) progression, but whether the ATRQβ‐001 vaccine would prevent AAA is unknown.Methods and ResultsAng II‐infused ApoE−/− mice and calcium phosphate‐induced AAA in C57BL/6 mice were used to verify the efficiency of ATRQβ‐001 vaccine in AAA. Results demonstrated that the vaccine effectively restrained the aneurysmal dilation and vascular wall destruction of aorta in both animal models, beyond anti‐hypertensive effects. In Ang II‐induced AAA vascular sections, Immunohistochemical staining showed that the vaccine notably constrained vascular inflammation and vascular smooth muscle cell (VSMC) phenotypic transition, concurrently reduced macrophages infiltration. In cultured VSMC, the anti‐ATR‐001 antibody inhibited osteopontin secretion induced by Ang II, thereby impeded macrophage migration while co‐culture. Furthermore, metalloproteinases and other matrix proteolytic enzymes were also found to be limited by the vaccine in vivo and in vitro.Conclusions ATRQβ‐001 vaccine prevented AAA initiation and progression in both Ang II and calcium phosphate‐induced AAA models. And the beneficial effects were played beyond decrease of blood pressure, which provided a novel and promising method to take precautions against AAA.

Targeted Therapy in Cardiovascular Disease: A Precision Therapy Era

“…In Liao's et al studies, the ATRQβ-001 vaccine could effectively decrease the blood pressure in the AngII induced hypertension mice and spontaneous hypertensive rats (SHRs) (Chen et al, 2013). The team also used ATRQβ-001 to treat AngII or calcium phosphateinduced abdominal aortic aneurysm (Zhang et al, 2019). The results showed that ATRQβ-001 could reduce blood pressure and inhibit the expansion of aneurysm and the destruction of the aortic wall in both models.…”

Immunotherapy against angiotensin II receptor ameliorated insulin resistance in a leptin receptor‐dependent manner

“…ATRQβ-001 vaccine and McAb-ATR were prepared as previously described. 21,22 Briefly, ATR-001 peptide (C-A-F-H-Y-E-S-Q) with a purity above 98% was synthesized and validated by GL Biochem Ltd (Shanghai, China). Qβ viruslike particle (VLP) was expressed and purified, then identified using SDS-PAGE and transmission electron microscopy.…”

“…RNA isolation, cDNA synthesis, quantitative real-time PCR (qRT-PCR), protein extraction, and western blotting were performed as previously described. 22 The primer sequences are listed in the Table S1. Cycle quantification (Cq) values of qRT-PCR were normalized by 18srRNA, calculated using the 2 −ΔΔCq method, and compared as arbitrary units.…”

“…21 Furthermore, the anti-ATR-001 monoclonal antibody (McAb-ATR) against ATRQβ-001 could specifically bind to AT1R and inhibit Ang II-AT1R signaling. 22 Here, to explore novel immunotherapy for insulin resistance, we evaluated the therapeutic effects of ATRQβ-001 vaccine and McAb-ATR on insulin resistance in ob/ob mice, then verified the efficacy of ATRQβ-001 in high-fat diet-induced obese (DIO) mice. Importantly, by comparing the effects McAb-ATR had on insulin sensitivity and leptin signaling between ob/ob and db/ db mice, we confirmed the important role of LepRb in the beneficial effects of McAb-ATR.…”

“…Targeting AT1R, we have developed an antihypertensive vaccine (ATRQβ‐001), which was proven to suppress AT1R activation and decrease blood pressure 21 . Furthermore, the anti‐ATR‐001 monoclonal antibody (McAb‐ATR) against ATRQβ‐001 could specifically bind to AT1R and inhibit Ang II‐AT1R signaling 22 . Here, to explore novel immunotherapy for insulin resistance, we evaluated the therapeutic effects of ATRQβ‐001 vaccine and McAb‐ATR on insulin resistance in ob/ob mice, then verified the efficacy of ATRQβ‐001 in high‐fat diet‐induced obese (DIO) mice.…”