title: Deletion of Periostin Protects Against Atherosclerosis in Mice by Altering Inflammation and Extracellular Matrix Remodeling.
abstract: OBJECTIVE
  Periostin is a secreted protein that can alter extracellular matrix remodeling in response to tissue injury. However, the functional role of periostin in the development of atherosclerotic plaques has yet to be described despite its observed induction in diseased vessels and presence in the serum.
  
  
  RESULTS
  Hyperlipidemic, apolipoprotein E-null mice (ApoE(-/) (-)) were crossed with periostin (Postn(-/-)) gene-deleted mice and placed on a high-fat diet for 6 or 14 weeks to induce atherosclerosis. En face analysis of aortas showed significantly decreased lesion areas of ApoE(-/-) Postn(-/-) mice compared with ApoE(-/-) mice, as well as a reduced inflammatory response with less macrophage content. Moreover, diseased aortas from ApoE(-/-) Postn(-/-) mice displayed a disorganized extracellular matrix with less collagen cross linking and smaller fibrotic caps, as well as increased matrix metalloproteinase-2, metalloproteinase-13, and procollagen-lysine, 2-oxoglutarate 5-dioxygenase-1 mRNA expression. Furthermore, the loss of periostin was associated with a switch in vascular smooth muscle cells toward a more proliferative and synthetic phenotype. Mechanistically, the loss of periostin reduced macrophage recruitment by transforming growth factor-β in cellular migration assays.
  
  
  CONCLUSIONS
  These are the first genetic data detailing the function of periostin as a regulator of atherosclerotic lesion formation and progression. The data suggest that periostin could be a therapeutic target for atherosclerotic plaque formation through modulation of the immune response and extracellular matrix remodeling.
authors.affiliation: From the Department of Pediatrics (J.A.S., A.L., R.J.V., D.V., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Schwanekamp
authors.affiliation: From the Department of Pediatrics (J.A.S., A.L., R.J.V., D.V., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH.
authors.forename: Angela
authors.initials: A
authors.lastname: Lorts
authors.affiliation: From the Department of Pediatrics (J.A.S., A.L., R.J.V., D.V., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Vagnozzi
authors.affiliation: From the Department of Pediatrics (J.A.S., A.L., R.J.V., D.V., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH.
authors.forename: Davy
authors.initials: D
authors.lastname: Vanhoutte
authors.affiliation: From the Department of Pediatrics (J.A.S., A.L., R.J.V., D.V., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH. Jeff.Molkentin@cchmc.org.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D066253:Vascular Remodeling
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse; D012333:RNA, Messenger; D003094:Collagen
keywords: apolipoproteins E; atherosclerosis; extracellular matrix; periostin