Increased expression of inflammation cytokines in senescent vascular smooth muscle cells by balloon catheter denudation is associated with NF-kappaB pathway

摘要

Objective: To determine whether balloon catheter denudation can induce vascular smooth muscle cells (VSMCs) to senescence, and whether this senescence can result in inflammation activity. Methods: Twelve male Chinese white rabbits were denuded of the carotid arteries or VSMCs. Acidic 13-galactosidase activity of carotid arteries or VSMCs was detected. Transfection and chloramphenicol acetyltransferase (CAT) assay for iNOS gene and nitrite (NO2-) assay were undertaken. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate inflammation cytokines mRNA expression. Measurement of NF-κB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9, ICAM-1, P-p65, and IκBα expressions were analyzed by Western blotting. Results: After denudation, VSMCs from denuded arteries showed an accumulation of significantly more senescence-associated β-galactosidase (SA-β-Gal) positive cells and greater iNOS activity. Transcriptional activity of iNOS was highly expressed. The mRNA expressions of IL-1β, 1CAM-1,MMP-9, TNF-α and the iNOS enzyme were significantly increased in injuring-induced senescence SMCs. However, the TNF-α or IL-1β-induced the protein production (ICAM-1 and MMP-9) was prevented by PDTC and MG132, which are inhibitors of NF-κB activation. Also, activation of NF-κB and cytokine-induced degradation of IκBα in the denuded VSMC were significantly affected. Conclusion: Intraluminal injury to the artery may lead to the emergence of senescent VSMC. Inflammation activity in SMCs is closely related to the senescence and the activation of NF-κB is involved.