Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 4000 Central Florida BLVD, Orlando, FL 32816, USA.
Mol Cell Biochem. 2013 Jan;372(1-2):267-73. doi: 10.1007/s11010-012-1468-7. Epub 2012 Oct 3.
Recent studies suggest that disturbed blood flow-induced shear stress can induce atherosclerosis (ATH) in humans and animals without a high fat diet. Therefore, we hypothesize that partial ligation of the left carotid artery can generate disturbed blood flow and shear stress and would lead to ATH in a predisposed genetic model of Apo E(-/-) mice. The partial left carotid artery model was generated by ligating three out of four branches of the left carotid artery compared with controls which experienced similar surgery conditions but no ligation. Animals were sacrificed 2 weeks post-ligation and examined for plaque formation, infiltration of leukocytes, pro-inflammatory immune response, and blood flow velocity. Our findings suggest a significant (p < 0.05) increase in plaque formation and lipid deposition in the partial ligated animals compared with controls, confirmed with hematoxylin and eosin and oil red O staining. Furthermore, there was a significant (p < 0.05) increase in the number of M1 macrophages and release of pro-inflammatory cytokines, IL-6 and TNFα, as compared with the control. Moreover, partial ligated carotid arteries demonstrated disturbed blood flow as their systolic velocity was significantly reduced. In conclusion, our data suggest that partial ligation of the left carotid artery induces disturbed flow and shear stress in the predisposed genetic model of Apo E(-/-) mice and leads to significantly developed ATH. Similarities to clinical patients who develop ATH independent of a high fat diet show that this could be a potential animal model to examine various parameters in ATH.
最近的研究表明，血流紊乱引起的切应力可在没有高脂饮食的情况下诱导人类和动物发生动脉粥样硬化（ATH）。因此，我们假设通过结扎左侧颈总动脉的部分分支，可以产生血流紊乱和切应力，并在载脂蛋白 E 基因敲除（Apo E(-/-)）小鼠的易感遗传模型中导致 ATH。通过结扎左侧颈总动脉的 4 个分支中的 3 个分支来建立左侧颈动脉部分结扎模型，对照组则接受了类似的手术条件但没有结扎。结扎后 2 周处死动物，检查斑块形成、白细胞浸润、促炎免疫反应和血流速度。我们的研究结果表明，与对照组相比，结扎组的斑块形成和脂质沉积明显增加（p<0.05），苏木精和伊红（H&E）以及油红 O 染色证实了这一点。此外，与对照组相比，M1 巨噬细胞的数量和促炎细胞因子 IL-6 和 TNFα 的释放也显著增加（p<0.05）。此外，结扎后的左侧颈总动脉血流紊乱，收缩期速度明显降低。总之，我们的数据表明，左侧颈总动脉部分结扎在 Apo E(-/-) 小鼠的易感遗传模型中引起了血流紊乱和切应力，并导致了明显发展的 ATH。与独立于高脂饮食发生 ATH 的临床患者的相似性表明，这可能是一个研究 ATH 各种参数的潜在动物模型。
