Oxidative stress-induced cellular senescence desensitizes cell growth and migration of vascular smooth muscle cells through down-regulation of platelet-derived growth factor receptor-beta

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.

ATF3 drives senescence by reconstructing accessible chromatin profiles

“…Among them, FOXA1, PLAT, CD44, FGF5, DIO2 and other genes are upregulated, whereas PLCB1, SETBP1, EHD3, ZNF423, PHGDH and other genes are downregulated in multiple senescence systems(Chan et al, 2019; Cho et al, 2019; Galanos et al, 2016; Hari et al, 2019; Hernandez-Segura et al, 2017; Komseli et al, 2018; Lau, Porciuncula, Yu, Iwakura, & David, 2019; Leveque et al, 2019; Q. Li et al, 2013; Limbad et al, 2020; Lowe & Raj, 2014; Nagano et al, 2016; Pan et al, 2019; Pantazi et al, 2019; Suwan et al, 2009; Wu, Pepowski, Takahashi, & Kron, 2019; Zhou et al, 2010), as are consistent with our results. These genes are located in or near the regions of IARs or DARs respectively.…”

Metabolism of vascular smooth muscle cells in vascular diseases

“…In rodent studies, the aortic tissues from aged mice exhibit mitochondrial dysfunction, and both cellular and mitochondrial levels of ROS are elevated in aortic tissues and VSMCs from aged mice (237,243). VSMCs from aged mice display several characteristics, including a reduced proliferation and migration, an alteration in the response to contracting mediators, and a shift from "contractile" to "synthetic" phenotype (46,178). Senescence aortic SMCs also exhibit mitochondrial DNA damage, increased ROS generation, increased lipid peroxidation, and decreased GSH and GSSG concentrations (165).…”

Biological aging mediates the associations between urinary metals and osteoarthritis among U.S. adults

“…Our results showed that both single (Cd, Co, Cs, Pb, and Tl) and mixed metals were positively associated with biological aging. Consistent toxicological evidence presented that heavy metals can induce senescence in stromal and vascular smooth muscle cells (e.g., Co and Cd) [35,36], as well as accelerate brain aging in animals, shown by damaged molecules and impaired energy metabolism [17]. Also, a recent population study indicated the positive associations between heavy metals (e.g., Co) and biological aging marker (DNA methylation age) [37].…”