1\. Introduction and derivation of the question Atherosclerosis is a major health problem. It is the most important underlying cause of cardiovascular disease, which is the main cause of death among European men under 65 and the second most common cause of death among European women. Atherosclerosis is a chronic, slowly progressing, non-reversible disease affecting the blood vessel walls leading to a "hardening" or "stiffening" of the arteries. The etiopathological connection between

more »

... osis and high blood cholesterol levels has been established in many studies. Different animal models have been used to explore the underlying mechanisms and characteristics of this disease and have generated inconsistent results. The lipid profiles of these models were often different to that observed in the human atherogenic lipid profile and thus did not appropriately reflect the pathogenesis of human atherosclerosis. Recently, the B6;129S-ApoBtm2SgyLdlrtm1Her mouse (ApoB mouse) was developed. It is an atherosclerotic double-knock-out low-density- lipoprotein-receptor-deficient apolipoprotein-B-100-only mouse. This mouse model has a lipid profile similar to most humans suffering from atherosclerosis. Using the ApoB mouse model, we explored the changes in vasoreactivity during the process of atherosclerotic alteration. For a further characterization of this mouse model, lipid profile and adhesion molecules were measured and morphometric evaluation of the research vessels was performed. 2\. Materials and methods Male ApoB mice and B6129SF2/J mice (B6 wild type, control mice) were examined at age 4 months (young group) or 18 months (old group). 2 mm ring preparations of the root of the aorta thoracica and of the main branch of the arteria mesenterica superior were mounted on tungsten wires into separate organ chambers of a myograph (Mulvany apparatus). Vessels were kept at 36.7°C in a physiological Krebs-Henseleit solution. Contraction was measured under isometric conditions. Phenylephrine, angiotensin II, acetylcholine (wi [...]