Departments of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA, USA.
Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
Physiol Rep. 2021 Jun;9(11):e14829. doi: 10.14814/phy2.14829.
Ligation of the common carotid artery near its bifurcation in apolipoprotein E-deficient (Apoe ) mice leads to rapid atherosclerosis development, which is affected by genetic backgrounds. BALB/cJ (BALB) mice are resistant to atherosclerosis, developing much smaller aortic lesions than C57BL/6 (B6) mice. In this study, we examined cellular events leading to lesion formation in carotid arteries with or without blood flow restriction of B6 and BALB Apoe mice. Blood flow was obstructed by ligating the left common carotid artery near its bifurcation in one group of mice, and other group received no surgical intervention. Without blood flow interruption, BALB-Apoe mice formed much smaller atherosclerotic lesions than B6-Apoe mice after 12 weeks of Western diet (3,325 ± 1,086 vs. 81,549 ± 9,983 µm /section; p = 2.1E-7). Lesions occurred at arterial bifurcations in both strains. When blood flow was obstructed, ligated carotid artery of both strains showed notable lipid deposition, inflammatory cell infiltration, and rapid plaque formation. Neutrophils and macrophages were observed in the arterial wall of BALB mice 3 days after ligation and 1 week after ligation in B6 mice. CD4 T cells were observed in intimal lesions of BALB but not B6 mice. By 4 weeks, both strains developed similar sizes of advanced lesions containing foam cells, smooth muscle cells, and neovessels. Atherosclerosis also occurred in straight regions of the contralateral common carotid artery where MCP-1 was abundantly expressed in the intima of BALB mice. These findings indicate that the disturbed blood flow is more prominent than high fat diet in promoting inflammation and atherosclerosis in hyperlipidemic BALB mice.
载脂蛋白 E 缺陷（Apoe）小鼠颈总动脉分叉附近结扎导致快速动脉粥样硬化发展，这受遗传背景的影响。BALB/cJ（BALB）小鼠对动脉粥样硬化具有抗性，其主动脉病变比 C57BL/6（B6）小鼠小得多。在这项研究中，我们研究了导致载脂蛋白 E 缺陷的 B6 和 BALB 小鼠颈总动脉出现病变的细胞事件，这些事件有或没有血流限制。通过在一组小鼠的颈总动脉分叉附近结扎来阻断血流，而另一组则不进行手术干预。在没有血流中断的情况下，BALB-Apoe 小鼠在 12 周的西方饮食后形成的动脉粥样硬化病变比 B6-Apoe 小鼠小得多（3325±1086μm/节对 81549±9983μm/节；p=2.1E-7）。两种品系的病变均发生在动脉分叉处。当血流受阻时，两种品系的结扎颈动脉均显示出明显的脂质沉积、炎症细胞浸润和快速斑块形成。在结扎后 3 天和 B6 小鼠结扎后 1 周，在 BALB 小鼠的动脉壁中观察到中性粒细胞和巨噬细胞。在 BALB 小鼠的内膜病变中观察到 CD4 T 细胞，但在 B6 小鼠中未观察到。4 周时，两种品系均形成了含有泡沫细胞、平滑肌细胞和新血管的大小相似的晚期病变。在 BALB 小鼠的内膜中，MCP-1 大量表达，在对侧颈总动脉的直段也发生了动脉粥样硬化。这些发现表明，在高脂血症 BALB 小鼠中，血流紊乱比高脂肪饮食更能促进炎症和动脉粥样硬化的发生。
