Deficiency of B vitamins leads to cholesterol-independent atherogenic transformation of the aorta

Background: Atherosclerosis, the leading cause of cardiovascular disease responsible for the majority of deaths worldwide, cannot be sufficiently explained by established risk factors including hypercholesterolemia. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. However, the role of homocysteine in atherosclerosis is still insufficiently understood. Previous research in this area has been also hampered by the lack of reproducible in-vivo models of atherosclerosis that resemble the human situation.Methods: Aortic specimens obtained from balloon injured rabbits fed either diet deficient in B vitamins, supplemented with 1% cholesterol or combined diet were subjected to ex vivo MRI, myographical, biomechanical, microscopical and histological analysis. Lipoproteins were analyzed by FPLC.Findings: We developed and applied an automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development even at low balloon pressure. Already in the absence of hypercholesterolemia, B vitamin deficiency results in accumulation of macrophages and lipids in the aorta, impairment of its biomechanical properties and disorganization of aortic collagen. Combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity of the aorta.Interpretation: Our findings suggest that deficiency of B vitamins leads to atherosclerotic transformation of the aorta already in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.Funding: This work was funded by the Austrian Science Fund (FWF) (Projects P31105 and P33672), the EU project NanoAthero and BioTechMed-Graz.