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导致动脉粥样硬化的主要因素，并且已经表明在斑块形成之前很明显。小阻力动脉的内皮功能障碍已被认为在导管动脉变化之前很久就开始了。在这项研究中，我们解决了动脉粥样硬化易感大鼠内皮功能的早期变化。雄性 ApoE 敲除 (KO) 大鼠（11 至 13 周大）接受西方饮食或标准饮食。饮食干预持续了 20-24 周。使用等长肌动仪在体外检查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合酶 (COX) 对控制肺动脉和肠系膜动脉血管张力的贡献。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、低密度脂蛋白和甘油三酯水平升高有关。在喂食西方饮食的 ApoE KO 大鼠的主动脉弓中也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，可以帮助我们改进临床前药物开发。