Accelerated atherogenesis in completely ligated common carotid artery of apolipoprotein E-deficient mice

Abstract

Complete ligation of the common carotid artery near its bifurcation induces neointimal formation due to smooth muscle cell proliferation in normolipidemic wild-type mice, but it was unknown what would happen to hyperlipidemic apolipoprotein E-deficient (Apoe-/-) mice. Examination of these mice revealed rapid development of atherosclerotic lesions in completely ligated carotid arteries within 4 weeks. Mice were fed a Western diet, starting 1 week before ligation, or a chow diet. Foam cell lesions formed as early as 1 week after ligation in mice fed the Western diet and 2 weeks in mice fed the chow diet. Fibrous lesions comprised of foam cells and smooth muscle cells and more advance lesions containing neovessels occurred at 2 and 4 weeks after ligation, respectively, in the Western diet group. Lesions were larger and more advanced in the Western diet group than the chow group. Neutrophil infiltration was observed in growing intimal lesions in both diet groups, while CD8+ T cells were found in lesions of chow-fed mice. This study demonstrates that Apoe-/- mice develop the entire spectrum of atherosclerosis in ligated carotid arteries in an accelerated manner and this model could be a valuable tool for investigating the development and therapy of atherosclerosis.

Response to the Letter to the Editor “The Relationship Between Neutrophil–Lymphocyte Ratio and In-Stent Restenosis”

“…2,14 In an animal experiment, we found that hyperlipidemia, which induces an inflammatory state, accelerated carotid intimal hyperplasia in Apoe −/− mice. 15 There was an increased neutrophil and CD8+ T cell adhesion and exudation, 15 supporting our finding on the association of NLR with restenosis.…”

“…Diabetes and hyperlipidemia are known risk factors for atherosclerosis and restenosis. 14,15 Our study also found a significantly higher incidence of early ISR in diabetic patients than nondiabetic patients. 13 The proportion of diabetic patients in the high baseline NLR group (NLR ≥ 3.62) was significantly higher than that of the lower baseline NLR group (NLR < 3.62).…”

Reactive Oxygen Species (ROS), Intimal Thickening, and Subclinical Atherosclerotic Disease

“…Several studies have shown upregulation of NOX-based NAD(P)H oxidases during the progression of AIT following flow restriction due to carotid injury (111) and lipid diet (112). The importance of intimal thickening to subclinical atherosclerosis in advancing atherosclerosis has been clearly established in ApoE gene deficient mice fed on a western diet in combination with carotid artery ligation-induced injury (113, 114).…”

Mice lacking global Stap1 expression do not manifest hypercholesterolemia

“…Obesity and insulin resistance are commonly associated with hyperlipidemia and high caloric fat- enriched diets are widely accepted to induce hyperlipidemia [ 26 ]. A western-type diet (TD.88137) was chosen for these studies for its ability to induce hypercholesterolemia, obesity and atherosclerosis depending on the genetic background of the mice used for study [ 24 , 27 , 28 ]. Previous studies have shown that 16 weeks of WD regime is sufficient to induce severe hypercholesterolemia in mice [ 29 , 30 ].…”