title: Agonistic antibody to angiotensin II type 1 receptor accelerates atherosclerosis in ApoE-/- mice.
abstract: This study aimed to investigate the effects of agonistic antibody to angiotensin II type 1 receptor (AT1-AA) on atherosclerosis in male ApoE-/- mice which were employed to establish the animal models of AT1-AA in two ways. In the first group, mice were injected subcutaneously with conjugated AT1 peptide at multiple sites; in the second group, mice were infused with AT1-AA prepared from rabbits that were treated with AT1 peptide intraperitoneally. Mice in each group were further randomly divided into five subgroups and treated with AT1 peptide/AT1-AA, AT1 peptide/AT1-AA plus valsartan, AT1 peptide/AT1-AA plus fenofibrate, AT1 peptide/ AT1-AA plus pyrrolidine dithiocarbamate (PDTC) and control vehicle, respectively. Antibodies were detected in mice (except for mice in control group). Aortic atherosclerotic lesions were assessed by oil red O staining, while plasma CRP, TNF-α, nuclear factor-kappa B (NF-κB) and H2O2 were determined by ELISA. CCR2 (the receptor of MCP-1), macrophages, and smooth muscle cells were detected by immunohistochemistry. P47phox, MCP-1 and eNOS were detected by RT-PCR, while P47phox, NF-κB and MCP-1 were detected by Western blot assay. The aortic atherosclerotic lesions were significantly increased in AT1 peptide/AT1-AA treated mice, along with simultaneous increases in inflammatory parameters. However, mice treated with valsartan, fenofibrate or PDTC showed alleviated progression of atherosclerosis and reductions in inflammatory parameters. Thus, AT1-AA may accelerate aortic atherosclerosis in ApoE-/- mice, which is mediated, at least in part, by the inflammatory reaction involving nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species, and NF-κB. In addition, valsartan, fenofibrate and PDTC may inhibit the AT1-AA induced atherosclerosis.
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Weijuan
authors: W
authors: Li
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Yaoqi
authors: Y
authors: Chen
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Songhai
authors: S
authors: Li
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Xiaopeng
authors: X
authors: Guo
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Wenping
authors: W
authors: Zhou
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Qiutang
authors: Q
authors: Zeng
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Yuhua
authors: Y
authors: Liao
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.
authors: Yumiao
authors: Y
authors: Wei
keywords: Agonistic antibody to angiotensin II type 1 receptor; atherosclerosis; inflammation
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