title: Neointima formed by arterial smooth muscle cells expressing versican variant V3 is resistant to lipid and macrophage accumulation.
abstract: OBJECTIVE
  Extracellular matrix (ECM) of neointima formed following angioplasty contains elevated levels of versican, loosely arranged collagen, and fragmented deposits of elastin, features associated with lipid and macrophage accumulation. ECM with a low versican content, compact structure, and increased elastic fiber content can be achieved by expression of versican variant V3, which lacks chondroitin sulfate glycosaminoglycans. We hypothesized that V3-expressing arterial smooth muscle cells (ASMC) can be used to form a neointima resistant to lipid and macrophage accumulation associated with hypercholesterolemia.
  
  
  RESULTS
  ASMC transduced with V3 cDNA were seeded into ballooned rabbit carotid arteries, and animals were fed a chow diet for 4 weeks, followed by a cholesterol-enriched diet for 4 weeks, achieving plasma cholesterol levels of 20 to 25 mmol/L. V3 neointimae at 8 weeks were compact, multilayered, and elastin enriched. They were significantly thinner (57%) than control neointimae; contained significantly more elastin (118%), less collagen (22%), and less lipid (76%); and showed significantly reduced macrophage infiltration (85%). Mechanistic studies demonstrated that oxidized low-density lipoprotein stimulated the formation of a monocyte-binding ECM, which was inhibited in the presence of V3 expressing ASMC.
  
  
  CONCLUSIONS
  These results demonstrate that expression of V3 in vessel wall creates an elastin-rich neointimal matrix that in the presence of hyperlipidemia is resistant to lipid deposition and macrophage accumulation.
authors: Department of Anatomy with Radiology, School of Medical Sciences, University of Auckland, Auckland, New Zealand. m.merrilees@auckland.ac.nz
authors: Mervyn J
authors: MJ
authors: Merrilees
authors: Brent W
authors: BW
authors: Beaumont
authors: Kathleen R
authors: KR
authors: Braun
authors: Anita C
authors: AC
authors: Thomas
authors: Inkyung
authors: I
authors: Kang
authors: Aleksander
authors: A
authors: Hinek
authors: Alberto
authors: A
authors: Passi
authors: Thomas N
authors: TN
authors: Wight
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000633:toxicity; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D053675:Versicans / Q000032:analysis / Q000502:physiology*
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D053675:Versicans