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Philipp Sievers,1 Lorenz Uhlmann,2 Sevil Korkmaz-Icöz,3 Christian Fastner,1 Florian Bea,1 Erwin Blessing,1 Hugo A Katus,1 Michael R Preusch11Department of Internal Medicine III, 2Institute of Medical Biometry and Informatics, 3Department of Cardiac Surgery, University of Heidelberg, Heidelberg, GermanyIntroduction: Besides their blood pressure-lowering effects, olmesartan medoxomil and amlodipine besylate exhibit additional anti-inflammatory mechanisms in atherosclerosic disease. Most of the studies investigating the effects of atherosclerosis focused on early atherosclerotic lesions, whereas lesions in human disease, at the time when medical treatment is started, are already well established. Therefore, we set up a model of advanced atherosclerosis and investigated the effects of olmesartan medoxomil, amlodipine besylate, and the combination of both on atherosclerotic lesion size and lesion composition.Materials and methods: Olmesartan medoxomil (1 mg/kg/day), amlodipine besylate (1.5 mg/kg/day), and the combination of both was added to chow and was fed to apolipoprotein E-deficient (ApoE-/-) mice at 25 weeks of age. Mice were sacrificed after 25 weeks of drug administration and perfused with formalin. Innominate arteries were dissected out and paraffin embedded. Serial sections were generated, and lesion sizes and their composition – such as minimal thickness of the fibrous cap, size of the necrotic core, and presence of calcification – were analyzed. Electrophoretic mobility shift assays were used to detect DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB) in aortic tissue.Results: Treatment with the combination of olmesartan medoxomil and amlodipine besylate led to a significant reduction in atherosclerotic lesion size in ApoE-/- mice (olmesartan medoxomil/amlodipine besylate: 122,277±6,795 µm2, number [n]=14; versus control: 177,502±10,814 µm2, n=9; P |
