CD147 monoclonal antibody attenuates abdominal aortic aneurysm formation in angiotensin II-Infused apoE-/- mice

Background: Abdominal aortic aneurysm (AAA) is a life threatening vascular disease. Our previous study reported the upregulation of CD147 expression in human aortic aneurysms. Objective: In this study, we injected apoE-/- mice intraperitoneally with CD147 monoclonal antibody or IgG control antibody to observe its effect on Angiotensin II (AngII) induced AAA formation. Methods: ApoE-/- mice were randomly divided into an AngII+CD147 antibody group (n = 20) and an AngII+IgG antibody group (n = 20). The Alzet osmotic minipump was implanted subcutaneously into the backs of mice to infuse AngII (1000 ng/kg/min) for 28 days and subsequently treated with CD147 monoclonal antibody or control IgG mAb (10 & mu;g/mouse/day) beginning one day after surgery. Body weight, food intake, drinking volume and blood pressure were measured weekly throughout the study. After 4 weeks of injection, routine bloodwork measuring liver function, kidney function and lipid levels were recorded. Hematoxylin and eosin (H & E), Masson's trichrome, and Elastic van Gieson (EVG) staining were used to evaluate the pathological changes in blood vessels. In addition, Immunohistochemical assay was used to detect infiltration of inflammatory cells. Tandem mass tag (TMT)-based proteomic analysis was used to define differentially expressed proteins (DEPs) using a pvalue < 0.05 and fold change > 1.2 or < 0.83 as the threshold. Subsequently, we conducted protein-protein interaction (PPI) network and GO enrichment analysis to determine the core biological function altered after CD147 antibody injection. Results: The CD147 monoclonal antibody suppresses Ang II-induced AAA formation in apoE-/- mice and reduced aortic expansion, elastic lamina degradation, and inflammatory cells accumulation. Bioinformatics analysis showed that Ptk6, Itch, Casp3, and Oas1a were the hub DEPs. These DEPs in the two group were mainly involved in collagen fibril organization, extracellular matrix organization, and muscle contraction. These data robustly demonstrated that CD147 monoclonal antibody suppresses Ang II-induced AAA formation through reduction of inflammatory response and regulation of the above defined hub proteins and biological processes. Thus, the CD147 monoclonal antibody might be a promising target in the treatment of abdominal aortic aneurysm.

Automated summary

In this study, it was found that CD147 monoclonal antibody effectively suppresses Ang II-induced AAA formation in apoE-/- mice by reducing aortic expansion, elastic lamina degradation, and inflammatory cells accumulation. Protein-protein interaction analysis revealed that Ptk6, Itch, Casp3, and Oas1a were the hub differentially expressed proteins, which were mainly involved in collagen fibril organization, extracellular matrix organization, and muscle contraction. Therefore, CD147 monoclonal antibody may be a promising target for the treatment of abdominal aortic aneurysm.