title: Thrombospondin-1 is elevated with both intimal hyperplasia and hypercholesterolemia.
abstract: BACKGROUND
  Thrombospondin-1 (TSP-1) is important in platelet adhesion and aggregation, inflammation, cell to cell interaction, angiogenesis, and smooth muscle cell (SMC) proliferation. TSP-1 expression increases rapidly with injury. Therefore, we hypothesize that TSP-1 may play a role in the development of intimal hyperplasia (IH). The purpose of this study is to examine the interaction between cholesterol and TSP-1 on SMC proliferation and to quantitatively assess TSP-1 expression in an established model of IH, with and without underlying cholesterol-induced atherosclerosis.
  
  
  METHODS
  In vitro, rabbit aortic SMC culture studies were performed to see the effect of TSP-1 antibodies on PDGF and, separately, cholesterol-induced SMC proliferation. In vivo, 23 rabbits were fed either a regular or a high-cholesterol diet. Hypercholesterolemia was confirmed by measurement of serum levels. Subsets underwent intraluminal aortic injury. Aortas were harvested 8-10 weeks later. Arterial wall TSP-1 was evaluated immunohistochemically and quantified by computer image analysis.
  
  
  RESULTS
  In vitro, TSP-1 antibodies were able to inhibit PDGF and cholesterol-induced SMC proliferation (P < 0.05). In vivo, TSP-1 was found predominantly in the extracellular matrix in the rabbit aorta. IH was uniformly seen status-post angioplasty. Hyperplasia was more prominent in samples from hypercholesterolemic animals. ANOVA and Student's t test analyses demonstrated significantly more TSP-1 in the high-cholesterol/angioplasty group than in all other groups (P = 0.0006 vs regular diet/no angioplasty group).
  
  
  CONCLUSIONS
  These data are consistent with the hypothesis that TSP-1 contributes to the development of IH. This study suggests that injured arteries in hypercholesterolemic atherosclerotic rabbits overexpress TSP-1.
authors.affiliation: Department of Surgery, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Roth
authors.forename: V
authors.initials: V
authors.lastname: Gahtan
authors.forename: J L
authors.initials: JL
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Gerhard
authors.forename: V K
authors.initials: VK
authors.lastname: Swami
authors.forename: V L
authors.initials: VL
authors.lastname: Rothman
authors.forename: T N
authors.initials: TN
authors.lastname: Tulenko
authors.forename: G P
authors.initials: GP
authors.lastname: Tuszynski
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism*; D006965:Hyperplasia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011817:Rabbits; D019700:Thrombospondin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D010982:Platelet-Derived Growth Factor; D019700:Thrombospondin 1