Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Division of General Neurology, Department of Neurology, Medical University of Graz, Graz, Austria; Division of Pediatric Radiology, Department of Radiology, Medical University of Graz, Graz, Austria.
Biomed Pharmacother. 2022 Oct;154:113640. doi: 10.1016/j.biopha.2022.113640. Epub 2022 Sep 5.
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. Here, we have 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. Our automated system helped to glean vital details of cholesterol-independent changes in the aortic wall of balloon-injured rabbits. We show that deficiency of B vitamins, which are required for homocysteine degradation, leads to atherogenic transformation of the aorta resulting in accumulation of macrophages and lipids, impairment of its biomechanical properties and disorganization of aortic collagen/elastin in the absence of hypercholesterolemia. A combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity compared to any single condition. Our findings suggest that deficiency of B vitamins leads to atherogenic transformation of the aorta even in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.
动脉粥样硬化是心血管疾病的主要病因，也是导致全球大多数人死亡的主要原因，其不能仅用已确立的风险因素（包括高胆固醇血症）来充分解释。血浆同型半胱氨酸升高是动脉粥样硬化的独立危险因素，与心血管死亡率密切相关。然而，同型半胱氨酸在动脉粥样硬化中的作用仍未被充分了解。该领域的先前研究也受到缺乏类似于人类情况的可重现的动脉粥样硬化体内模型的阻碍。在这里，我们开发并应用了一种自动化的血管壁损伤系统，该系统可导致更均匀的损伤和更明显的动脉粥样硬化斑块发展，即使在低球囊压力下也是如此。我们的自动化系统有助于深入了解胆固醇非依赖性损伤对球囊损伤兔主动脉壁的影响。我们发现，同型半胱氨酸降解所需的 B 族维生素缺乏会导致主动脉发生动脉粥样硬化转化，从而导致巨噬细胞和脂质的积累、生物力学特性受损以及主动脉胶原/弹性蛋白的紊乱，而无需高胆固醇血症。与任何单一条件相比，B 族维生素缺乏症和高胆固醇血症的组合会导致主动脉变厚、主动脉水扩散减少、LDL-胆固醇增加和血管反应性受损。我们的研究结果表明，即使在没有高胆固醇血症的情况下，B 族维生素缺乏也会导致主动脉发生动脉粥样硬化转化，并在其存在的情况下加重动脉粥样硬化的发展。
