title: The effects of diet on occlusive coronary artery atherosclerosis and myocardial infarction in scavenger receptor class B, type 1/low-density lipoprotein receptor double knockout mice.
abstract: OBJECTIVE
  Deficiency of the high-density lipoprotein receptor, scavenger receptor class B, type I (SR-BI), in apolipoprotein E knockout or hypomorphic mice, respectively, results in spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis, myocardial infarction, and early death. Here, we examine effects of SR-BI deficiency on cardiovascular phenotypes in low-density lipoprotein receptor (LDLR) knockout mice fed different atherogenic diets.
  
  
  RESULTS
  SR-BI/LDLR double knockout and control LDLR knockout mice were fed atherogenic diets containing different amounts of fat, cholesterol, and sodium cholate. Double knockout mice fed atherogenic diets high in cholesterol exhibited significantly reduced survival compared with LDLR knockout mice fed the same diets. In addition to increased diet-accelerated aortic sinus atherosclerosis, we observed significant diet-induced CA atherosclerosis in double knockout mice and diet-dependent accumulation of platelets in CA atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Atherogenic diet fed double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of Ly6C(hi) and Ly6C(int) monocytes, and higher adhesion molecule expression in CA endothelial cells compared with control LDLR knockout mice.
  
  
  CONCLUSIONS
  Diet-accelerated atherosclerosis and occlusive, platelet-rich CA disease in SR-BI/LDLR double knockout mice is affected by amounts of cholesterol and cholate in atherogenic diets and is accompanied by increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CAs and increased Ly6C(hi) and Ly6C(int) monocytes in circulation. The increased vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CA endothelial cells in SR-BI-deficient mice likely explains their increased susceptibility to atherosclerosis in CAs.
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Mark
authors.initials: M
authors.lastname: Fuller
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Omid
authors.initials: O
authors.lastname: Dadoo
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Viktoria
authors.initials: V
authors.lastname: Serkis
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Dina
authors.initials: D
authors.lastname: Abutouk
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Melissa
authors.initials: M
authors.lastname: MacDonald
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Neel
authors.initials: N
authors.lastname: Dhingani
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Joseph
authors.initials: J
authors.lastname: Macri
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.).
authors.forename: Suleiman A
authors.initials: SA
authors.lastname: Igdoura
authors.affiliation: From the Departments of Biochemistry and Biomedical Sciences (M.F., O.D., V.S., D.A., M.M., N.D., B.L.T.), Pathology and Molecular Medicine (J.M., S.A.I.), and Biology (S.A.I.), McMaster University, Hamilton, Ontario, Canada; and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (M.F., O.D., V.S., M.M., N.D., B.L.T.). trigatt@mcmaster.ca.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Trigatti
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000453:epidemiology* / Q000378:metabolism; D020355:Cholates / Q000009:adverse effects; D002791:Cholesterol, Dietary / Q000009:adverse effects; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004036:Diet, Atherogenic / Q000009:adverse effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D015994:Incidence; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D012307:Risk Factors; D051122:Scavenger Receptors, Class B / Q000172:deficiency* / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D020355:Cholates; D002791:Cholesterol, Dietary; D016207:Cytokines; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
keywords: HDL; atherosclerosis; receptors, lipoprotein; thrombosis