Inflammation and enhanced atherogenesis in the carotid artery with altered blood flow in an atherosclerosis‐resistant mouse strain

Physiological Reports

Andrew T. Grainger¹  Zhaoyu Liu²  Weibin Shi³  Zhihui Chang³  Chaoji Huangfu³  Jian Zhao³  Wei Zhou³ 

[1] Biochemistry & Molecular Genetics University of Virginia Charlottesville Virginia USA;Department of Radiology Shengjing Hospital of China Medical University Shenyang China;Departments of Radiology & Medical Imaging University of Virginia Charlottesville VA USA;

关键词: atherosclerosis;    blood flow;    carotid artery;    genetic background;    hyperlipidemia;   

DOI  :  10.14814/phy2.14829

来源: DOAJ

【 摘 要 】

Abstract 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 µm2/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.

【 授权许可】

Unknown