PMID- 11015350
OWN - NLM
STAT- MEDLINE
DCOM- 20001026
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 102
IP  - 14
DP  - 2000 Oct 3
TI  - Direct evidence for cytokine involvement in neointimal hyperplasia.
PG  - 1697-702
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 
      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-alpha 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-alpha and IL-1alpha mRNA demonstrated both TNF-alpha and 
      IL-1alpha mRNA in ligated CCAs, whereas normal and sham-operated CCAs had none. 
      Mice lacking functional TNF-alpha (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-1alpha mRNA expression was detected in CCAs from TNF-/- mice; 
      however, TNF-alpha mRNA expression was found in the IL-1RI-/- mice. Mice that 
      overexpress membrane-bound TNF-alpha but produce no soluble TNF-alpha display an 
      accentuated fibroproliferative response to low shear stress (P:<0.05). 
      CONCLUSIONS: These results directly demonstrate that TNF-alpha and IL-1 modulate 
      NIH induced by low shear stress. NIH can proceed by way of soluble 
      TNF-alpha-independent mechanisms. Specific anti-TNF-alpha and anti-IL-1 therapies 
      may lessen NIH.
FAU - Rectenwald, J E
AU  - Rectenwald JE
AD  - University of Florida College of Medicine, Malcom Randall VAMC, Gainesville, FL, 
      USA.
FAU - Moldawer, L L
AU  - Moldawer LL
FAU - Huber, T S
AU  - Huber TS
FAU - Seeger, J M
AU  - Seeger JM
FAU - Ozaki, C K
AU  - Ozaki CK
LA  - eng
GR  - 1T32-GM08721-01/GM/NIGMS NIH HHS/United States
GR  - GM-40586/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Interleukin-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Hyperplasia/metabolism
MH  - Immunohistochemistry
MH  - Interleukin-1/genetics/metabolism/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Tumor Necrosis Factor-alpha/metabolism/*physiology
MH  - Tunica Intima/metabolism/*pathology
EDAT- 2000/10/04 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/04 11:00
PHST- 2000/10/04 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/04 11:00 [entrez]
AID - 10.1161/01.cir.102.14.1697 [doi]
PST - ppublish
SO  - Circulation. 2000 Oct 3;102(14):1697-702. doi: 10.1161/01.cir.102.14.1697.