Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse smooth muscle cells in atherosclerosis-prone and resistant regions of the aorta of C57Bl/6 mice at age of 4 months

ABSTRACT: This study compared gene expression in smooth muscle cells (SMCs) in atherosclerosis-prone and atherosclerosis-resistant regions of the aorta of C57Bl/6 mice. In a parallel experiment, both regions were compared in young, plaque-free apolipoprotein E-deficient (apoE-/-) mice. Aortas of 3 male and 3 female C57Bl6 mice were isolated, perfused with triton X-100 to remove endothelial cells and divided in an atherosclerosis-prone region (AA: ascending aorta, aortic arch and proximal 2 mm of thoracic aorta) and an atherosclerosis-resistant region (TA: central thoracic aorta,i.e. 6 mm distal from the proximal 2mm of the thoracic aorta). Microarray analysis (VIB-MAF) of pooled total RNA showed differential expression (>2-fold difference) for 70 genes. Up- or downregulation in the AA was observed for 33 and 37 genes respectively. Differential expression of 3 genes (ATPase, Na+/K+ transporting, beta 1 polypeptide, sarcolipin and homeo box B7) was confirmed using real-time PCR. Twenty five genes showed exclusively differential expression in C57BL6 mice. Only 7 could be linked to specific processes: development (4) and cell growth (3). The other 18 genes were all involved in different processes. Among the 45 genes showing differential expression in C57Bl/6 as well as apoE-/- mice, most were related to development (13), cell growth (8) and transcription (10). These results point to an altered transcriptome in SMCs of the C57Bl/6 aorta at an atherosclerosis-prone location. This is in agreement with findings in endothelial cells in atherosclerosis-prone regions. It could be due to biomechanical differences, for instance in wall tension or shear stress, or the different embryological origin of SMCs in AA and TA. Experiment Overall Design: Samples were hybridized in dye-swap design.

ORGANISM(S): Mus musculus

SUBMITTER: Joke Allemeersch

PROVIDER: E-GEOD-13835 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Smooth muscle cells (SMCs) are important in a number of physiological systems and organs, including the cardiovascular system. The hallmark property of differentiated SMCs is the ability to contract, but contractile SMCs themselves show a range of phenotypes allowing prolonged tonic contraction in vascular smooth muscle or rapid phasic contraction in tissues such as bladder. Another distinctive characteristic, in contrast with terminally differentiated striated muscle cells, is that SMCs exhibit phenotypic plasticity. Vascular SMCs are able to modulate their phenotype along a continuum between a contractile phenotype, characteristic of healthy blood vessels, and a more proliferative âsyntheticâ phenotype, so-named for the enhanced synthesis and secretion of extracellular matrix components. Synthetic phenotype cells are found in a number of pathological situations such as atherosclerosis and arterial injury. We used mouse exon-junction (MJAY) arrays to gain insights into both the global contribution of alternative splicing events in re-shaping the transcriptome of dedifferentiating mouse aorta and bladder SMCs, and into the underlying regulatory mechanisms of the alternative splicing program. Affymetrix splice junction arrays (MJAY) were used to profile changes in both alternative splicing and transcript levels during the phenotypic modulation of smooth muscle cells when placed in culture. RNA extracted from intact aorta and bladder smooth muscle tissue was used for differentiated samples. For dedifferentiated, proliferative samples smooth muscle cells were enzymatically dispersed and grown in tissue culture for a week. Triplicate RNA samples were prepared from smooth muscle tissue of mouse aorta and bladder (differentiated) and from smooth muscle cells from each tissue cultured for 7 days (proliferative). The samples allowed comparison of alternative splicing (and other transcriptome) changes between differentiated and proliferative smooth muscle cell samples from two distinct types of smooth muscle cell, as well as allowing direct comparison of aorta (tonic smooth muscle) and bladder (phasic smooth muscle).

Project description:We adopted a transcriptome-wide microarray analysis approach to determine the extent to which vascular gene expression is altered as a result of juvenile obesity and identify obesity-responsive mRNAs. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n=5) and lean (n=6) juvenile Ossabaw pigs (age=22 weeks). Obesity was experimentally induced by feeding the animals a high-fat/high fructose corn syrup/high-cholesterol diet for 16 weeks. We found that expression of 189 vascular cell genes in the LAD and expression of 165 genes in the thoracic aorta were altered with juvenile obesity (FDRM-bM-^IM-$10%) with an overlap of only 28 genes between both arteries. Notably, a number of genes found to be markedly up-regulated in the LAD of obese pigs are implicated in atherosclerosis, including ACP5, LYZ, CXCL14, APOE, PLA2G7, LGALS3, SPP1, ITGB2, CYBB, and P2RY12. Furthermore, pathway analysis revealed the induction of pro-inflammatory and pro-oxidant pathways with obesity primarily in the LAD. Gene expression in the LAD perivascular fat was minimally altered with juvenile obesity. Together, we provide new evidence that obesity produces artery-specific changes in pre-translational regulation with a clear up-regulation of pro-atherogenic genes in the LAD. Our data may offer potential viable drug targets and mechanistic insights regarding the molecular precursors involved in the origins of over-nutrition and obesity-associated vascular disease. In particular, our results suggest that the oxLDL-LOX-1-NFM-NM-:B signaling axis may be involved in the early initiation of a juvenile obesity-induced pro-atherogenic coronary artery phenotype. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n=5) and lean (n=6) juvenile Ossabaw pigs (age= 22 weeks). All three tissue types were taken from each animal, and each was applied to one and only one array array except a single Thoracic aorta (Animal ID 63 because there were not enough arrays), so there were 32 total arrays (11 unique pigs).

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Transcription profiling of mouse smooth muscle cells in atherosclerosis-prone and resistant regions of the aorta of C57Bl/6 mice at age of 4 months

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