Dotted collar placed around carotid artery induces asymmetric neointimal lesion formation in rabbits without intravascular manipulations

Abstract

BackgroundNeointimal formation in atherosclerosis has been subject for intense research. However, good animal models mimicking asymmetrical lesion formation in human subjects have been difficult to establish. The aim of this study was to develop a model which would lead to the formation of eccentric lesions under macroscopically intact non-denuded endothelium.MethodsWe have developed a new collar model where we placed two cushions or dots inside the collar. Arterial lesions were characterized using histology and ultrasound methods.ResultsWhen this dotted collar was placed around carotid and femoral arteries it produced asymmetrical pressure on adventitia and a mild flow disturbance, and hence a change in shear stress. Our hypothesis was that this simple procedure would reproducibly produce asymmetrical lesions without any intraluminal manipulations. Intima/media ratio increased towards the distal end of the collar with the direction of blood flow under macroscopically intact endothelium. Macrophages preferentially accumulated in areas of the thickest neointima thus resembling early steps in human atherosclerotic plaque formation. Proliferating cells in these lesions and underlying media were scarce at eight weeks time point.ConclusionThe improved dotted collar model produces asymmetrical human-like atherosclerotic lesions in rabbits. This model should be useful in studies regarding the pathogenesis and formation of eccentric atherosclerotic lesions.