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

Abstract

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 β-galactosidase activity of carotid arteries or VSMCs was detected. Transfection and chloramphenicol acetyltransferase (CAT) assay for iNOS gene and nitrite (NO 2 −) 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, ICAM-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.