title: Amino terminal 38.9% of apolipoprotein B-100 is sufficient to support cholesterol-rich lipoprotein production and atherosclerosis.
abstract: OBJECTIVE
  Carboxyl terminal truncation of apolipoprotein (apo)B-100 and apoB-48 impairs their capacity for triglyceride transport, but the ability of the resultant truncated apoB to transport cholesterol and to support atherosclerosis has not been adequately studied. The atherogenicity of apoB-38.9 was determined in this study by using our apoB-38.9-only (Apob38.9/38.9) mice.
  
  
  RESULTS
  ApoB-38.9-lipoproteins (Lp-B38.9) circulate at very low levels in Apob38.9/38.9 mice as small LDLs or HDLs. Disruption of apoE gene in these mice caused accumulation of large amounts of betaVLDL-like LpB-38.9 in plasma. These betaVLDL particles were more enriched with cholesteryl esters but poor in triglycerides compared with the apoB-48-betaVLDL of the apoB-wild-type/apoE-null (Apob+/+/Apoe-/-) mice. Likewise, apoB-38.9-VLDL secreted by cultured Apob38.9/38.9 mouse hepatocytes also had higher ratios of total cholesterol to triglycerides than apoB-48-VLDL secreted by the apoB-48-only hepatocytes. Thus, despite its impaired triglyceride-transporting capacity, apoB-38.9 has a relatively intact capacity for cholesterol transport. Spontaneous aortic atherosclerotic lesions were examined in apoB-38.9-only/apoE-null (Apob38.9/38.9/Apoe-/-) mice at ages 9 and 13 months. Extensive lesions were found in the Apob38.9/38.9/Apoe-/- mice as well as in their Apob+/38.9/Apoe-/- and Apob+/+/Apoe-/- littermates.
  
  
  CONCLUSIONS
  Deleting the C-terminal 20% from apoB-48 does not impair its ability to transport cholesterol and to support atherosclerosis, thus narrowing the "atherogenic region" of apoB.
authors.affiliation: Department of Medicine, Washington University School of Medicine, Box 8046, 660 South Euclid Avenue, St Louis, MO 63110, USA. zchen@im.wustl.edu
authors.forename: Zhouji
authors.initials: Z
authors.lastname: Chen
authors.forename: Robin L
authors.initials: RL
authors.lastname: Fitzgerald
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Saffitz
authors.forename: Clay F
authors.initials: CF
authors.lastname: Semenkovich
authors.forename: Gustav
authors.initials: G
authors.lastname: Schonfeld
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000378:metabolism / Q000473:pathology; D001055:Apolipoproteins B / Q000737:chemistry* / Q000502:physiology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000378:metabolism; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013047:Specific Pathogen-Free Organisms; D013329:Structure-Activity Relationship
chemical_list: D001055:Apolipoproteins B; D001057:Apolipoproteins E; D015243:Cholesterol, VLDL; D010446:Peptide Fragments; D002784:Cholesterol