BACKGROUND/AIMS: Site-specific atherosclerosis is generally attributed to differential gene expression in endothelial cells. We investigated whether the transcriptome of smooth muscle cells is different between atherosclerosis-prone and atherosclerosis-resistant regions in apolipoprotein E-deficient (apoE-/-) mice before plaque development, and in C57Bl/6 mice. METHODS: De-endothelialized aortas (both strains: 3 males, 3 females, age 4 months) were divided into atherosclerosis-prone (AA: ascending aorta, aortic arch and proximal 2 mm of thoracic aorta) and -resistant (CTA: central thoracic aorta, i.e. 6 mm distal from the proximal 2 mm) regions. The transcriptome of these two regions was compared using whole-genome mouse microarrays. RESULTS: Microarray analysis revealed differential expression (>2-fold difference) of 70 and 244 genes in C57Bl/6 and apoE-/- mice. This was confirmed for 6 genes using the real-time quantitative polymerase chain reaction. Up- or downregulation in the AA was observed for 33 and 37 genes in C57Bl/6, and for 186 and 58 genes in apoE-/- mice, respectively. The 201 genes that showed exclusively differential expression in apoE-/- mice were related to atherosclerotic processes, such as cell adhesion, proliferation, differentiation, motility, cell death, lipid metabolism and immune responses. CONCLUSION: Our findings indicate that smooth muscle cells display an altered transcriptome at atherosclerosis-prone locations before actual lesion development.
BACKGROUND/AIMS: Site-specific atherosclerosis is generally attributed to differential gene expression in endothelial cells. We investigated whether the transcriptome of smooth muscle cells is different between atherosclerosis-prone and atherosclerosis-resistant regions in apolipoprotein E-deficient (apoE-/-) mice before plaque development, and in C57Bl/6 mice. METHODS: De-endothelialized aortas (both strains: 3 males, 3 females, age 4 months) were divided into atherosclerosis-prone (AA: ascending aorta, aortic arch and proximal 2 mm of thoracic aorta) and -resistant (CTA: central thoracic aorta, i.e. 6 mm distal from the proximal 2 mm) regions. The transcriptome of these two regions was compared using whole-genome mouse microarrays. RESULTS: Microarray analysis revealed differential expression (>2-fold difference) of 70 and 244 genes in C57Bl/6 and apoE-/- mice. This was confirmed for 6 genes using the real-time quantitative polymerase chain reaction. Up- or downregulation in the AA was observed for 33 and 37 genes in C57Bl/6, and for 186 and 58 genes in apoE-/- mice, respectively. The 201 genes that showed exclusively differential expression in apoE-/- mice were related to atherosclerotic processes, such as cell adhesion, proliferation, differentiation, motility, cell death, lipid metabolism and immune responses. CONCLUSION: Our findings indicate that smooth muscle cells display an altered transcriptome at atherosclerosis-prone locations before actual lesion development.
Authors: Saske Hoving; Sylvia Heeneman; Marion J J Gijbels; Johannes A M te Poele; Manlio Bolla; Jeffrey F C Pol; Michelle Y Simons; Nicola S Russell; Mat J Daemen; Fiona A Stewart Journal: PLoS One Date: 2010-09-21 Impact factor: 3.240
Authors: Fernanda B Fusco; Diego J Gomes; Kely C S Bispo; Veronica P Toledo; Denise F Barbeiro; Vera L Capelozzi; Luzia N S Furukawa; Ana P P Velosa; Walcy R Teodoro; Joel C Heimann; Eder C R Quintao; Marisa Passarelli; Edna R Nakandakare; Sergio Catanozi Journal: PLoS One Date: 2017-05-08 Impact factor: 3.240
Authors: Lina Dobnikar; Annabel L Taylor; Joel Chappell; Phoebe Oldach; Jennifer L Harman; Erin Oerton; Elaine Dzierzak; Martin R Bennett; Mikhail Spivakov; Helle F Jørgensen Journal: Nat Commun Date: 2018-11-01 Impact factor: 14.919