Department of Clinical Medicine, Aarhus University, Palle Juul Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU Norwegian University of Science and Technology, Trondheim, Norway.
Sci Rep. 2020 Sep 17;10(1):15296. doi: 10.1038/s41598-020-72338-3.
Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclerosis prone rats. Male ApoE knockout (KO) rats (11- to 13-weeks-old) were subjected to either a Western or standard diet. The diet intervention continued for a period of 20-24 weeks. Endothelial function of pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. Chondroid-transformed smooth muscle cells, calcifications, macrophages accumulation and foam cells were also observed in the aortic arch from ApoE KO rats fed Western diet. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development.
内皮功能障碍被认为是动脉粥样硬化的主要原因，并被认为早在斑块形成之前就已经存在。小阻力动脉的内皮功能障碍被认为早在导管动脉发生变化之前就已经开始。在这项研究中，我们研究了易患动脉粥样硬化的大鼠的内皮功能早期变化。雄性载脂蛋白 E 基因敲除 (KO) 大鼠 (11-13 周龄) 分别给予西方饮食或标准饮食。饮食干预持续 20-24 周。使用等长肌描记法在体外研究肺和肠系膜动脉的内皮功能。我们发现，西方饮食降低了环氧化酶 (COX) 对肺和肠系膜动脉血管张力的控制作用。这些变化与 ApoE KO 大鼠的早期动脉粥样硬化和血浆总胆固醇、LDL 和甘油三酯水平升高有关。在西方饮食喂养的 ApoE KO 大鼠的主动脉弓中还观察到软骨样转化的平滑肌细胞、钙化、巨噬细胞积聚和泡沫细胞。ApoE KO 大鼠是研究动脉粥样硬化早期内皮功能障碍的新模型，有助于我们改善临床前药物开发。
