Abstract
The relationship between aging and restenosis are unclear. The purposes of this study were to investigate the possible pathological role and mechanism of aging on formation of restenosis. Our data indicated that cell proliferation and migration of the oxidative stress-induced senescent vascular smooth muscle cells were obviously desensitized to stimulation by platelet-derived growth factor (PDGF)-BB, which may have been caused by suppression of promoter activity, transcription, translation, and activation levels of PDGF receptor (PDGFR)-β. The analyzed data obtained from the binding array of transcription factors (TFs) showed that binding levels of eighteen TFs on the PDGFR-β promoter region (-523 to -1) were significantly lower in senescent cells compared to those of non-senescent cells. Among these TFs, the bioinformatics prediction suggested that the putative binding sites of ten TFs were found in this promoter region. Of these, transcriptional levels of seven TFs were markedly reduced in senescent cells. The clinical data showed that the proportion of restenosis was relatively lower in the older group than that in the younger group. Our study results suggested that a PDGFR-β-mediated pathway was suppressed in aging cells, and our clinical data showed that age and the vascular status were slightly negatively correlated in overall participants.
Highlights
The proportion of the population that is aging has been increasing yearly worldwide, which is mainly attributed to improvements in healthcare and reductions in fertility rates
Our results showed that binding levels of 18 transcription factors (TFs) obviously decreased (>2-fold difference) in senescent cells compared to those of normal cells (Table 1)
Results obtained from rodent studies showed that arterial oxidative stress was significantly higher in aged groups [11,12,13]
Summary
The proportion of the population that is aging has been increasing yearly worldwide, which is mainly attributed to improvements in healthcare and reductions in fertility rates. Intracellular reactive oxygen species (ROS) or free radicals are mainly produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or leak from the mitochondrial electron transport chain. The progressive accumulation of ROS can induce oxidative stress and damage normal functions of macromolecules, such as nucleic acids, proteins, and lipids, resulting in some detrimental effects, e.g., mutations of nucleic acids, deactivation or destruction of proteins, and lipid peroxidation. Cobalt dichloride (CoCl2) was found to promote oxidative stress by producing free radicals in vivo and in vitro as well as mimicking chemical hypoxia by preventing the degradation of the intrinsic hypoxia marker, hypoxia-inducible factor (HIF)-1α [3,4,5].
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