Deletion of Sema4D gene reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice
Neovascularization occurring in atherosclerotic plaque leads to acceleration of plaque growth through increased leukocyte infiltration and reactive oxygen species (ROS) production. Sema4D (CD100), a class IV semaphorin, not only plays a crucial role in axon guidance but also functions in the neovascularization process of tumor growth. To clarify the roles of Sema4D in the progression of atherosclerosis and neovascularization of atherosclerotic plaque, we analyzed the effect of Sema4D gene deletion from apolipoprotein E (ApoE)-deficient mice in the development of atherosclerosis. Lipid staining demonstrated significant decreases in plaque areas in the aortas of 6-month-old Sema4D−/−ApoE−/− mice compared with 6-month-old ApoE−/− mice. Thus, the Sema4D gene knockout in ApoE-deficient mice was found to slow the progression of atherosclerosis. Immunohistochemical analyses confirmed the expression of Sema4D protein in infiltrating lymphoid cells in atherosclerotic plaque and plexin-B1 receptor in neovascular endothelial cells within the plaque. Furthermore, there were significant decreases in the degree of neovascularization in the plaque areas of Sema4D−/−ApoE−/− mice compared with ApoE−/− mice as revealed by both isolectin B4 and CD31 staining. The number of infiltrating macrophages in Sema4D−/−ApoE−/− mice plaques was also significantly less than those in ApoE−/− mice. These findings suggest that Sema4D is involved in the progression phase of atherosclerosis by accelerating intimal neovascularization, resulting in enhanced macrophage infiltration in atherosclerotic plaques.
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Document Type: Research Article
Affiliations: Department of Physiology, Faculty of Pharmacy, Meijo University, Nagoya 468-8503, Japan., Email: [email protected]
Publication date: July 1, 2010
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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