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Berger, O., Gan, X., Gujuluva, C., Burns, A.R., Sulur, G., Stins, M., Way, D., Witte, M., Weinand, M., Said, J., Kim, K.S., Taub, D., Graves, M.C. and Fiala, M. (1999) CXC and CC chemokine receptors on coronary and brain endothelia. Molecular Medicine, 5, 795-805.

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• TITLE: Anti eotaxin-2 antibodies attenuate the initiation and progression of experimental atherosclerosis

  AUTHORS: Adi Mor, Arnon Afek, Michal Entin-Meer, Gad Keren, Jacob George

  KEYWORDS: Atherosclerosis; Vulnerable Plaque; Inflammation; Eotaxin-2; Chemokines

  JOURNAL NAME: World Journal of Cardiovascular Diseases, Vol.3 No.4, July 18, 2013

  ABSTRACT: Background: The chemokine eotaxin-2 is a potent chemoattractant for inflammatory cells, the predominants of which are eosinophils. Human and murine atherosclerotic plaques are known to exhibit inflammatory phenotypes where a complex interaction of cytokine and chemokines plays a role. We tested the hypothesis that eotaxin-2 (eo-2) plays a causative role in the initiation and progression of experimental atherosclerosis. Methods and Results: Sera collected from atherosclerotic ApoE knockout (KO) mice, exhibited significantly higher levels of eo-2 compared to sera collected from their background age matched C57BL/6 litters by ELISA. Moreover, levels of eo-2 were higher in old atherosclerotic ApoE KO mice than in young animals. Similarly, the expression level of the eo-2 receptor, CCR3, was increased in splenocytes of old ApoE compared to the young littermates. Administration of polyclonal blocking antibodies to eotaxin-2 resulted in a significant reduction of early atherosclerotic plaques in ApoE KO mice whereas prolonged treatment of mice with advanced plaques led to atheroma stabilization. A monoclonal antibody (D8) prepared against eo-2 attenuated adhesion of lymphocytes to fibronectin and potently inhibited their migration towards VEGF. Monoclonal blocking antibodies to eo-2 also significantly reduced atherosclerotic plaques in ApoE KO mice. Conclusion: Eo-2 serum levels are elevated in sera of ApoE KO mice with experimental atherosclerosis and its blockade is associated with reduced fatty streak accumulation and increased plaque stabilization.