Direct evidence for cytokine involvement in neointimal hyperplasia

Article

关键词: TUMOR-NECROSIS-FACTOR;    SMOOTH-MUSCLE CELLS;    FACTOR-ALPHA;    DEFICIENT MICE;    TNF-ALPHA;    CAROTID-ARTERY;    IN-VITRO;    INTERLEUKIN-1;    ATHEROSCLEROSIS;    EXPRESSION;   

DOI  :  10.1161/01.CIR.102.14.1697

来源: SCIE

【 摘 要 】

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-1 alpha mRNA demonstrated both TNF-alpha and IL-1 alpha 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-1 alpha 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.

【 授权许可】

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