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

Dominick.G.A. Burton , Peter.J. Giles , Angela.N.P. Sheerin , S.Kaye Smith , Jessica.J. Lawton , Elizabeth.L. Ostler , William Rhys-Williams , David Kipling , Richard.G.A. Faragher

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 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 (-value < 0.5%, minimum effect size of at least 2-fold differential regulation, explore data at www.madras.cf.ac.uk/vsmc). 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 (IL1β, IL8, ICAM1, TNFAP3, ESM1 and CCL2), tissue remodelling (VEGF, VEGFβ, ADM and MMP14) and vascular calcification (MGP, BMP2, SPP1, OPG and DCN). The microarray data for IL1β, 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.

Mots clés: vascular calcification; atherosclerosis; cellular senescence; ageing; cardiovascular disease; vascular smooth muscle

Dominick.G.A. Burton, Peter.J. Giles, Angela.N.P. Sheerin, S.Kaye Smith, Jessica.J. Lawton, et al.. Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification. Experimental Gerontology, 2009, 44 (10), pp.659. ⟨10.1016/j.exger.2009.07.004⟩. ⟨hal-00520353⟩