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  • Title: Thrombospondin-1 is elevated with both intimal hyperplasia and hypercholesterolemia.
    Author: Roth JJ, Gahtan V, Brown JL, Gerhard C, Swami VK, Rothman VL, Tulenko TN, Tuszynski GP.
    Journal: J Surg Res; 1998 Jan; 74(1):11-6. PubMed ID: 9536966.
    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. MATERIALS AND 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.
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