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CD147 monoclonal antibody attenuates abdominal aortic aneurysm formation in angiotensin II-Infused apoE-/- mice
Cheng Xu1, Xiaowei Liu2, Lei Yu1
1Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou 317000, PR China.
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 μg/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 p-value < 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.
Insights
CD147 monoclonal antibody treatment effectively reduced abdominal aortic aneurysm (AAA) formation in mice. This targeted therapy suppressed inflammation and altered key proteins, showing promise for AAA treatment.
Area of Science:
- Vascular Biology
- Immunology
- Proteomics
Background:
- Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease.
- Previous research indicated elevated CD147 expression in human aortic aneurysms.
Purpose of the Study:
- To investigate the therapeutic effect of CD147 monoclonal antibody on Angiotensin II (AngII)-induced AAA formation in apolipoprotein E-deficient (apoE-/-) mice.
Main Methods:
- Administered CD147 monoclonal antibody or IgG control to apoE-/- mice infused with AngII.
- Monitored physiological parameters, performed histopathological analysis (H&E, Masson's, EVG), and conducted immunohistochemistry.
- Utilized Tandem mass tag (TMT)-based proteomic analysis to identify differentially expressed proteins (DEPs) and performed protein-protein interaction (PPI) network and Gene Ontology (GO) enrichment analysis.
Main Results:
- CD147 monoclonal antibody significantly suppressed AngII-induced AAA formation, reducing aortic expansion, elastic lamina degradation, and inflammatory cell infiltration.
- Proteomic analysis identified Ptk6, Itch, Casp3, and Oas1a as key differentially expressed proteins (DEPs) involved in extracellular matrix organization and muscle contraction.
- Bioinformatics analysis revealed that CD147 antibody treatment modulated inflammatory responses and regulated identified hub proteins and biological pathways.
Conclusions:
- CD147 monoclonal antibody demonstrates a therapeutic potential in mitigating AAA progression by reducing inflammation and regulating critical protein networks.
- The findings suggest that CD147 monoclonal antibody is a promising therapeutic target for abdominal aortic aneurysm treatment.
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