A Refined Injury and Modular Dietary Design for Studying Atherogenesis in Rabbits: The Next Level in Deciphering the Interplay of Risk Factors

Abstract Atherosclerosis is the leading cause of cardiovascular disease, which is responsible for the majority of deaths worldwide. Lack of reproducible and controlled induction of atherosclerotic lesions in preclinical animal models limits atherosclerosis research. Here, we developed the first automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development at low balloon pressure in a rabbit model of atherosclerosis, and used this system to investigate the risk factor interplay. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. Already in the absence of hypercholesterolemia, deficiency in vitamins and choline required for homocysteine metabolization results in atherogenic transformation of the aorta i.e. impairment of its biomechanical properties, alteration of collagen organization as well as macrophage and lipid accumulation, and aggravation of atherosclerosis including significantly altered water diffusion and impaired vascular reactivity in its presence.