title: Fibromodulin deficiency reduces low-density lipoprotein accumulation in atherosclerotic plaques in apolipoprotein E-null mice.
abstract: OBJECTIVE
  The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques.
  
  
  RESULTS
  Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes; inflammatory in low-shear stress regions and fibrous in oscillatory shear stress regions. Electron microscopy showed that collagen fibrils were thicker and more heterogeneous in oscillatory shear stress lesions from ApoE/fibromodulin-null mice. Low-shear stress lesions were smaller in ApoE/fibromodulin-null mice and contained less lipids. Total plaque burden in aortas stained en face with Oil Red O, as well as lipid accumulation in aortic root lesions, was also decreased in ApoE/fibromodulin-null mice. In addition, lipid accumulation in RAW264.7 macrophages cultured on fibromodulin-deficient extracellular matrix was decreased, whereas levels of interleukin-6 and -10 were increased. Our results show that an abnormal plaque collagen fibril structure can influence atherosclerotic plaque development.
  
  
  CONCLUSIONS
  The present findings suggest a more complex role for collagen in plaque stability than previously anticipated, in that it may promote lipid-accumulation and inflammation at the same time as it provides mechanical stability.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden. Annelie.Shami@med.lu.se
authors.forename: Annelie
authors.initials: A
authors.lastname: Shami
authors.forename: Renata
authors.initials: R
authors.lastname: Gustafsson
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kalamajski
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
authors.forename: Dolf
authors.initials: D
authors.lastname: Segers
authors.forename: Uwe
authors.initials: U
authors.lastname: Rauch
authors.forename: Gunnel
authors.initials: G
authors.lastname: Roos
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.forename: Åke
authors.initials: Å
authors.lastname: Oldberg
authors.forename: Anna
authors.initials: A
authors.lastname: Hultgårdh-Nilsson
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D002340:Carotid Artery Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics; D024022:Fibrillar Collagens / Q000378:metabolism / Q000648:ultrastructure; D000071235:Fibromodulin; D005838:Genotype; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics; D012039:Regional Blood Flow; D013314:Stress, Mechanical
chemical_list: D001057:Apolipoproteins E; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; C000604332:Fmod protein, mouse; C556062:IL10 protein, mouse; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D000071235:Fibromodulin; D016753:Interleukin-10