Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis.

Journal Article (Journal Article)

OBJECTIVE: Mechanisms by which tumor necrosis factor-alpha (TNF) contributes to atherosclerosis remain largely obscure. We therefore sought to determine the role of the arterial wall TNF receptor-1 (TNFR1) in atherogenesis. METHODS AND RESULTS: Carotid artery-to-carotid artery interposition grafting was performed with tnfr1-/- and congenic (C57Bl/6) wild-type (WT) mice as graft donors, and congenic chow-fed apolipoprotein E-deficient mice as recipients. Advanced atherosclerotic graft lesions developed within 8 weeks, and had 2-fold greater area in WT than in tnfr1-/- grafts. While the prevalence of specific atheroma cells was equivalent in WT and tnfr1-/- grafts, the overall abundance of cells was substantially greater in WT grafts. WT grafts demonstrated greater MCP-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 expression at both early and late time points, and proliferating cell nuclear antigen expression at early time points. Aortic atherosclerosis was also reduced in 14-month-old apoe(-/-)/tnfr1(-/-) mice, as compared with cognate apoe-/- mice. In coculture with activated macrophages, smooth muscle cells expressing the TNFR1 demonstrated enhanced migration and reduced scavenger receptor activity. CONCLUSIONS: TNFR1 signaling, just in arterial wall cells, contributes to the pathogenesis of atherosclerosis by enhancing arterial wall chemokine and adhesion molecule expression, as well as by augmenting medial smooth muscle cell proliferation and migration.

Full Text

Duke Authors

Cited Authors

  • Zhang, L; Peppel, K; Sivashanmugam, P; Orman, ES; Brian, L; Exum, ST; Freedman, NJ

Published Date

  • May 2007

Published In

Volume / Issue

  • 27 / 5

Start / End Page

  • 1087 - 1094

PubMed ID

  • 17442899

Pubmed Central ID

  • PMC2522308

Electronic International Standard Serial Number (EISSN)

  • 1524-4636

Digital Object Identifier (DOI)

  • 10.1161/ATVBAHA.0000261548.49790.63


  • eng

Conference Location

  • United States