Open AccessATRQ β‐001 Vaccine Prevents Experimental Abdominal Aortic Aneurysms
Author(s) -
Zhang Hongrong,
Liao Mengyang,
Cao Mingsi,
Qiu Zhihua,
Yan Xiaole,
Zhou Yanzhao,
Wu Hailang,
Wang Yingxuan,
Zheng Jiayu,
Ding Jiaxing,
Wang Min,
Liao Yuhua,
Chen Xiao
Publication year - 2019
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.119.012341
Subject(s) - medicine , vascular smooth muscle , abdominal aortic aneurysm , angiotensin ii , matrix metalloproteinase , adventitia , inflammation , aorta , immunology , blood pressure , pathology , aneurysm , smooth muscle , surgery
Background We have developed a peptide vaccine named ATRQ β‐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 ATRQ β‐001 vaccine would prevent AAA is unknown. Methods and Results Ang II ‐infused ApoE −/− mice and calcium phosphate‐induced AAA in C57 BL /6 mice were used to verify the efficiency of ATRQ β‐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 ATRQ β‐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 .