title: Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet.
abstract: BACKGROUND
  Mice deficient in the LDL receptor (Ldlr(-/-) mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time-points are yet to be established. The current study sought to determine the progression and distribution of lesions in Ldlr(-/-) mice.
  
  
  RESULTS
  Ldlr-deficient mice fed regular chow or a high-fat (HF) diet for 0.5 to 12 months were analyzed for atherosclerotic lesions with en face and cross-sectional imaging. Mice displayed significant individual differences in lesion development when fed a chow diet, whereas those on a HF diet developed lesions in a time-dependent and site-selective manner. Specifically, mice subjected to the HF diet showed slight atherosclerotic lesions distributed exclusively in the aortic roots or innominate artery before 3 months. Lesions extended to the thoracic aorta at 6 months and abdominal aorta at 9 months. Cross-sectional analysis revealed the presence of advanced lesions in the aortic sinus after 3 months in the group on the HF diet and in the innominate artery at 6 to 9 months. The HF diet additionally resulted in increased total cholesterol, LDL, glucose, and HBA1c levels, along with the complication of obesity.
  
  
  CONCLUSIONS
  Ldlr-deficient mice on the HF diet tend to develop site-selective and size-specific atherosclerotic lesions over time. The current study should provide information on diet induction or drug intervention times and facilitate estimation of the appropriate locations of atherosclerotic lesions in Ldlr(-/-) mice.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Ma
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Youli
authors.initials: Y
authors.lastname: Lu
authors.forename: Wenyu
authors.initials: W
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology*; D001786:Blood Glucose / Q000032:analysis; D016122:Brachiocephalic Trunk / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D018450:Disease Progression; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000209:etiology / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000473:pathology*; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013995:Time; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides