title: Scavenger Receptor Class B Type 1 Deletion Led to Coronary Atherosclerosis and Ischemic Heart Disease in Low-density Lipoprotein Receptor Knockout Mice on Modified Western-type Diet.
abstract: OBJECTIVE
  Atherosclerosis-prone apolipoprotein E (apoE) or low-density lipoprotein receptor (LDL-R) knockout (KO) mice are generally resistant to developing coronary atherosclerosis (CA) and ischemic heart disease (IHD). However, studies have demonstrated the occurrence of spontaneous CA and IHD in scavenger receptor class B type 1 (SR-BI)/apoE double KO (dKO) mice, which suggests that SR-BI could be a potential target for the prevention and therapy of CA and IHD. This possibility was later investigated in SR-BI/LDL-R dKO mice, but no signs of CA or IHD was identified when mice were fed a normal western-type diet. Here we explored whether SR-BI deletion could result in CA and IHD in LDL-R KO mice when fed a modified western-type diet containing higher (0.5%) cholesterol.
  
  
  METHODS
  Cardiac functions were detected by electrocardiography, single photon emission computed tomography (SPECT), echocardiography (Echo) and 2,3,5-triphenyltetrazolium chloride staining. CA was visualized by hematoxylin-eosin staining.
  
  
  RESULTS
  After 12 weeks on the modified diet, SR-BI/LDL-R dKO mice developed cardiac ischemia/infarction, together with systolic dysfunction and left ventricular dilatation. CA was most severe at the aortic sinus level to an extent that no dKO mice survived to 20 weeks on the modified diet. None of control mice, however, developed CA or IHD.
  
  
  CONCLUSIONS
  SR-BI deletion led to CA and IHD in LDL-R KO mice when fed the modified western-type diet. We established SR-BI/LDL-R dKO mice as a diet-induced murine model of human IHD and developed detection methods, using a combination of SPECT and Echo, for effective in vivo evaluation of cardiac functions.
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Liao
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Mengyu
authors.initials: M
authors.lastname: Wang
authors.forename: Chengyan
authors.initials: C
authors.lastname: Dong
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Abudurexiti
authors.initials: A
authors.lastname: Kayoumu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: George
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D003324:Coronary Artery Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004036:Diet, Atherogenic / Q000009:adverse effects*; D004562:Electrocardiography; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011973:Receptors, LDL / Q000502:physiology*; D051122:Scavenger Receptors, Class B / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B