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Mycophenolate mofetil as an immunomodulatory silver bullet in atherogenesis?

Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

J J P Kastelein

Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

M R Hayden

Centre for Molecular Medicine and Therapeutics, B.C. Children’s and Women’s Hospital, Department of Medical Genetics, University of British Columbia, Vancouver, Canada

E S Stroes

Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands, e.s.stroes{at}amc.uva.nl

Atherosclerotic vascular disease is a chronic disorder of the vasculature with a substantial impact on society. Although the availability of statins has represented an unparalleled improvement in the treatment of patients with such cardiovascular disease, even more effective measures are required to reverse this disorder with a continuously growing incidence. The classification of atherosclerosis as an inflammatory disorder has prompted the hypothesis that immunomodulation could comprise a novel anti-atherosclerotic strategy. Mycophenolate mofetil (MMF) has various anti-atherogenic effects on major components of the atherosclerotic plaque such as T-lymphocytes, monocytes/macrophages and the endothelium. MMF can inhibit leukocyte recruitment to the subendothelium and the subsequent reduced activation of leukocytes will translate into attenuation of subendothelial crosstalk between T-cells and macrophages. This cascade of events will interrupt the self-perpetuating pro-inflammatory environment within the arterial wall, the hallmark of atherosclerotic vascular disease.

Key Words: atherogenesis • MMF • leukocytes • endothelium • inflammation

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