Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification

University of Brighton, United Kingdom.
Experimental gerontology (Impact Factor: 3.49). 07/2009; 44(10):659-65. DOI: 10.1016/j.exger.2009.07.004
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Little is known about the senescent phenotype of human vascular smooth muscle cells (VSMCs) and the potential involvement of senescent VSMCs in age-related vascular disease, such as atherosclerosis. As such, VSMCs were grown and characterised in vitro to generate senescent VSMCs needed for microarray analysis (Affymetrix). Comparative analysis of the transcriptome profiles of early (14 CPD) and late (39-42 CPD) passage VSMCs found a total of 327 probesets called as differentially expressed: 149 are up-regulated in senescence and 178 repressed (p-value<0.5%, minimum effect size of at least 2-fold differential regulation, explore data at Data mining shows a differential regulation of genes at senescence associated with the development of atherosclerosis and vascular calcification. These included genes with roles in inflammation (IL1beta, IL8, ICAM1, TNFAP3, ESM1 and CCL2), tissue remodelling (VEGF, VEGFbeta, ADM and MMP14) and vascular calcification (MGP, BMP2, SPP1, OPG and DCN). The microarray data for IL1beta, IL8 and MGP were validated by either, ELISA, Western blot analysis or RT-PCR. These data thus provide the first evidence for a role of VSMC senescence in the development of vascular calcification and provides further support for the involvement of senescent VSMCs in the progression of atherosclerosis.

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Available from: Dominick G.A Burton, Sep 30, 2015
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    • "ismal lifespan entry into the senescent state probably prevents the growth of tumors , thus contributing to organismal survival . However , cellular senescence is typically associated with the heavily upregulated secretion of proinflammatory factors and other changes which have the potential to produce degenerative effects ( Coppé et al . , 2008 ; Burton et al . , 2009 ; Kipling et al . , 2009 ) . As a result of declining clearance rates with age senescent cells accumulate in multiple tissues with in vivo age in a variety of species ( Kipling et al . , 2004 ; Herbig et al . , 2006 ) . The best evidence that senescent cells play a causal role in aging is the recent observation that their ablation in a "
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    • "Endothelial cell (EC) and vascular smooth muscle cell (VSMC) senescence in particular has been linked to the development of cardiovascular disease, specifically atherosclerosis [1-3]. The senescent phenotype has been proposed to result in an impaired ability to replace damaged or lost cells or to produce altered tissue microenvironments within the vessel [4]. Accordingly we reviewed the available data on proliferative capacity, donor age and cardiovascular disease status with regard to these cell types, in order to produce a meta-dataset spanning a range of age groups and cardiovascular disease states, allowing provisional conclusions to be drawn. "
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    • "However, we did not see in aged human mammary arteries any regulation of RunX2, a key transcription factor in osteoblast differentiation, which participates in the VSMC calcifying process (Gaur et al., 2005; Byon et al., 2008; Speer et al., 2009). Altogether, our observations are in line with recent publications showing that senescent VSMC can transdifferentiate into osteochondrogenic precursors , an early step in vascular calcification (Burton et al., 2009; Nakano-Kurimoto et al., 2009; Speer et al., 2009). "
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