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

Lisheng Zhang, Karsten Peppel, Perumal Sivashanmugam, Eric Orman, Leigh Brian, Sabrina T. Exum, Neil J. Freedman

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

OBJECTIVE - Mechanisms by which tumor necrosis factor-α (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.

Original languageEnglish (US)
Pages (from-to)1087-1094
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume27
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Fingerprint

Tumor Necrosis Factor Receptors
Cell Wall
Atherosclerosis
Transplants
Apolipoproteins E
Carotid Arteries
Smooth Muscle Myocytes
Scavenger Receptors
Vascular Cell Adhesion Molecule-1
Proliferating Cell Nuclear Antigen
Atherosclerotic Plaques
Intercellular Adhesion Molecule-1
Coculture Techniques
Chemokines
Cell Movement
Tumor Necrosis Factor-alpha
Macrophages
Cell Proliferation

Keywords

  • Atherosclerosis
  • Inflammation
  • Mouse models
  • Smooth muscle cells
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis. / Zhang, Lisheng; Peppel, Karsten; Sivashanmugam, Perumal; Orman, Eric; Brian, Leigh; Exum, Sabrina T.; Freedman, Neil J.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 27, No. 5, 05.2007, p. 1087-1094.

Research output: Contribution to journalArticle

Zhang, Lisheng ; Peppel, Karsten ; Sivashanmugam, Perumal ; Orman, Eric ; Brian, Leigh ; Exum, Sabrina T. ; Freedman, Neil J. / Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2007 ; Vol. 27, No. 5. pp. 1087-1094.
@article{60f995e01a724952bd1f5a7f6fb95299,
title = "Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis",
abstract = "OBJECTIVE - Mechanisms by which tumor necrosis factor-α (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.",
keywords = "Atherosclerosis, Inflammation, Mouse models, Smooth muscle cells, Tumor necrosis factor",
author = "Lisheng Zhang and Karsten Peppel and Perumal Sivashanmugam and Eric Orman and Leigh Brian and Exum, {Sabrina T.} and Freedman, {Neil J.}",
year = "2007",
month = "5",
doi = "10.1161/ATVBAHA.0000261548.49790.63",
language = "English (US)",
volume = "27",
pages = "1087--1094",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis

AU - Zhang, Lisheng

AU - Peppel, Karsten

AU - Sivashanmugam, Perumal

AU - Orman, Eric

AU - Brian, Leigh

AU - Exum, Sabrina T.

AU - Freedman, Neil J.

PY - 2007/5

Y1 - 2007/5

N2 - OBJECTIVE - Mechanisms by which tumor necrosis factor-α (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.

AB - OBJECTIVE - Mechanisms by which tumor necrosis factor-α (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.

KW - Atherosclerosis

KW - Inflammation

KW - Mouse models

KW - Smooth muscle cells

KW - Tumor necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=34247383507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247383507&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.0000261548.49790.63

DO - 10.1161/ATVBAHA.0000261548.49790.63

M3 - Article

C2 - 17442899

AN - SCOPUS:34247383507

VL - 27

SP - 1087

EP - 1094

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 5

ER -