Direct evidence for cytokine involvement in neointimal hyperplasia

John E. Rectenwald, Lyle L. Moldawer, Thomas S. Huber, James M. Seeger, C. Keith Ozaki

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Background - Tumor necrosis factor-α (TNF-α) and interleukin 1 (IL-1) are proximal inflammatory cytokines that stimulate expression of adhesion molecules and induce synthesis of other proinflammatory cytokines. In addition, TNF-α and IL-1 influence vascular smooth muscle cell migration and proliferation in vitro. In view of the inflammatory nature of neointimal hyperplasia (NIH), we tested the hypothesis that endogenous TNF-α and IL-1 modulate low shear stress-induced NIH. Methods and Results - Mice underwent unilateral common carotid artery (CCA) ligation. Low shear stress in the patent ligated CCA has previously been shown to result in remodeling and NIH. Reverse transcriptase-polymerase chain reaction for TNF-α and IL-1α mRNA demonstrated both TNF-α and IL-1α mRNA in ligated CCAs, whereas normal and sham-operated CCAs had none. Mice lacking functional TNF-α (TNF-/-) developed 14-fold less neointimal area than WT controls (P<0.05). p80 IL-1 type I receptor knockout (IL-1RI-/-) mice tended to develop less (7-fold, P>0.05) neointimal area than WT controls. Furthermore, no IL-1α mRNA expression was detected in CCAs from TNF-/- mice; however, TNF-α mRNA expression was found in the IL-1RI-/- mice. Mice that overexpress membrane-bound TNF-α but produce no soluble TNF-α display an accentuated fibroproliferative response to low shear stress (P<0.05). Conclusions - These results directly demonstrate that TNF-α and IL-1 modulate NIH induced by low shear stress. NIH can proceed by way of soluble TNF-α-independent mechanisms. Specific anti-TNF-α and anti-IL-1 therapies may lessen NIH.

Original languageEnglish (US)
Pages (from-to)1697-1702
Number of pages6
JournalCirculation
Volume102
Issue number14
DOIs
StatePublished - Oct 3 2000

Fingerprint

Hyperplasia
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-1
Messenger RNA
Common Carotid Artery
Reverse Transcriptase Polymerase Chain Reaction
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Movement
Ligation
Cell Proliferation
Membranes

Keywords

  • Atherosclerosis
  • Carotid arteries
  • Remodeling
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Rectenwald, J. E., Moldawer, L. L., Huber, T. S., Seeger, J. M., & Ozaki, C. K. (2000). Direct evidence for cytokine involvement in neointimal hyperplasia. Circulation, 102(14), 1697-1702. https://doi.org/10.1161/01.CIR.102.14.1697

Direct evidence for cytokine involvement in neointimal hyperplasia. / Rectenwald, John E.; Moldawer, Lyle L.; Huber, Thomas S.; Seeger, James M.; Ozaki, C. Keith.

In: Circulation, Vol. 102, No. 14, 03.10.2000, p. 1697-1702.

Research output: Contribution to journalArticle

Rectenwald, JE, Moldawer, LL, Huber, TS, Seeger, JM & Ozaki, CK 2000, 'Direct evidence for cytokine involvement in neointimal hyperplasia', Circulation, vol. 102, no. 14, pp. 1697-1702. https://doi.org/10.1161/01.CIR.102.14.1697
Rectenwald JE, Moldawer LL, Huber TS, Seeger JM, Ozaki CK. Direct evidence for cytokine involvement in neointimal hyperplasia. Circulation. 2000 Oct 3;102(14):1697-1702. https://doi.org/10.1161/01.CIR.102.14.1697
Rectenwald, John E. ; Moldawer, Lyle L. ; Huber, Thomas S. ; Seeger, James M. ; Ozaki, C. Keith. / Direct evidence for cytokine involvement in neointimal hyperplasia. In: Circulation. 2000 ; Vol. 102, No. 14. pp. 1697-1702.
@article{c168940586dd4c25960c93d82760b23b,
title = "Direct evidence for cytokine involvement in neointimal hyperplasia",
abstract = "Background - Tumor necrosis factor-α (TNF-α) and interleukin 1 (IL-1) are proximal inflammatory cytokines that stimulate expression of adhesion molecules and induce synthesis of other proinflammatory cytokines. In addition, TNF-α and IL-1 influence vascular smooth muscle cell migration and proliferation in vitro. In view of the inflammatory nature of neointimal hyperplasia (NIH), we tested the hypothesis that endogenous TNF-α and IL-1 modulate low shear stress-induced NIH. Methods and Results - Mice underwent unilateral common carotid artery (CCA) ligation. Low shear stress in the patent ligated CCA has previously been shown to result in remodeling and NIH. Reverse transcriptase-polymerase chain reaction for TNF-α and IL-1α mRNA demonstrated both TNF-α and IL-1α mRNA in ligated CCAs, whereas normal and sham-operated CCAs had none. Mice lacking functional TNF-α (TNF-/-) developed 14-fold less neointimal area than WT controls (P<0.05). p80 IL-1 type I receptor knockout (IL-1RI-/-) mice tended to develop less (7-fold, P>0.05) neointimal area than WT controls. Furthermore, no IL-1α mRNA expression was detected in CCAs from TNF-/- mice; however, TNF-α mRNA expression was found in the IL-1RI-/- mice. Mice that overexpress membrane-bound TNF-α but produce no soluble TNF-α display an accentuated fibroproliferative response to low shear stress (P<0.05). Conclusions - These results directly demonstrate that TNF-α and IL-1 modulate NIH induced by low shear stress. NIH can proceed by way of soluble TNF-α-independent mechanisms. Specific anti-TNF-α and anti-IL-1 therapies may lessen NIH.",
keywords = "Atherosclerosis, Carotid arteries, Remodeling, Restenosis",
author = "Rectenwald, {John E.} and Moldawer, {Lyle L.} and Huber, {Thomas S.} and Seeger, {James M.} and Ozaki, {C. Keith}",
year = "2000",
month = "10",
day = "3",
doi = "10.1161/01.CIR.102.14.1697",
language = "English (US)",
volume = "102",
pages = "1697--1702",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "14",

}

TY - JOUR

T1 - Direct evidence for cytokine involvement in neointimal hyperplasia

AU - Rectenwald, John E.

AU - Moldawer, Lyle L.

AU - Huber, Thomas S.

AU - Seeger, James M.

AU - Ozaki, C. Keith

PY - 2000/10/3

Y1 - 2000/10/3

N2 - Background - Tumor necrosis factor-α (TNF-α) and interleukin 1 (IL-1) are proximal inflammatory cytokines that stimulate expression of adhesion molecules and induce synthesis of other proinflammatory cytokines. In addition, TNF-α and IL-1 influence vascular smooth muscle cell migration and proliferation in vitro. In view of the inflammatory nature of neointimal hyperplasia (NIH), we tested the hypothesis that endogenous TNF-α and IL-1 modulate low shear stress-induced NIH. Methods and Results - Mice underwent unilateral common carotid artery (CCA) ligation. Low shear stress in the patent ligated CCA has previously been shown to result in remodeling and NIH. Reverse transcriptase-polymerase chain reaction for TNF-α and IL-1α mRNA demonstrated both TNF-α and IL-1α mRNA in ligated CCAs, whereas normal and sham-operated CCAs had none. Mice lacking functional TNF-α (TNF-/-) developed 14-fold less neointimal area than WT controls (P<0.05). p80 IL-1 type I receptor knockout (IL-1RI-/-) mice tended to develop less (7-fold, P>0.05) neointimal area than WT controls. Furthermore, no IL-1α mRNA expression was detected in CCAs from TNF-/- mice; however, TNF-α mRNA expression was found in the IL-1RI-/- mice. Mice that overexpress membrane-bound TNF-α but produce no soluble TNF-α display an accentuated fibroproliferative response to low shear stress (P<0.05). Conclusions - These results directly demonstrate that TNF-α and IL-1 modulate NIH induced by low shear stress. NIH can proceed by way of soluble TNF-α-independent mechanisms. Specific anti-TNF-α and anti-IL-1 therapies may lessen NIH.

AB - Background - Tumor necrosis factor-α (TNF-α) and interleukin 1 (IL-1) are proximal inflammatory cytokines that stimulate expression of adhesion molecules and induce synthesis of other proinflammatory cytokines. In addition, TNF-α and IL-1 influence vascular smooth muscle cell migration and proliferation in vitro. In view of the inflammatory nature of neointimal hyperplasia (NIH), we tested the hypothesis that endogenous TNF-α and IL-1 modulate low shear stress-induced NIH. Methods and Results - Mice underwent unilateral common carotid artery (CCA) ligation. Low shear stress in the patent ligated CCA has previously been shown to result in remodeling and NIH. Reverse transcriptase-polymerase chain reaction for TNF-α and IL-1α mRNA demonstrated both TNF-α and IL-1α mRNA in ligated CCAs, whereas normal and sham-operated CCAs had none. Mice lacking functional TNF-α (TNF-/-) developed 14-fold less neointimal area than WT controls (P<0.05). p80 IL-1 type I receptor knockout (IL-1RI-/-) mice tended to develop less (7-fold, P>0.05) neointimal area than WT controls. Furthermore, no IL-1α mRNA expression was detected in CCAs from TNF-/- mice; however, TNF-α mRNA expression was found in the IL-1RI-/- mice. Mice that overexpress membrane-bound TNF-α but produce no soluble TNF-α display an accentuated fibroproliferative response to low shear stress (P<0.05). Conclusions - These results directly demonstrate that TNF-α and IL-1 modulate NIH induced by low shear stress. NIH can proceed by way of soluble TNF-α-independent mechanisms. Specific anti-TNF-α and anti-IL-1 therapies may lessen NIH.

KW - Atherosclerosis

KW - Carotid arteries

KW - Remodeling

KW - Restenosis

UR - http://www.scopus.com/inward/record.url?scp=0034601753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034601753&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.102.14.1697

DO - 10.1161/01.CIR.102.14.1697

M3 - Article

C2 - 11015350

AN - SCOPUS:0034601753

VL - 102

SP - 1697

EP - 1702

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 14

ER -