Project description:This study investigates the role of endothelial cell (EC) gene expression in the focal origin of atherosclerosis, particularly in response to local hemodynamics. Differential gene expression was profiled in EC isolated from athero-susceptible and athero-protected regions of the normal pig aorta. Specifically, a region of disturbed flow (DF, the inner aortic arch) was compared to a region of undisturbed flow (UF, descending thoracic aorta). Linearly amplified RNA was used to screen nylon filter arrays of 13,824 human cDNAs.
Project description:Comparisons of canine arterial gene expression between control and untreated MPS animals were conducted with a canine-specific microarray covering 43,803 probes (Agilent G2519F 4x44k, Santa Clara, CA), for a total of four comparison groups: MPS ascending aorta vs. control ascending aorta, MPS descending aorta vs. control descending aorta, MPS carotid artery vs. control carotid artery, and finally pooled MPS artery (ascending aorta, descending aorta, carotid artery) vs. pooled control artery. Each comparison used four pairs of MPS vs corresponding age- and gender- matched animals to produce four biologic replicates.
Project description:The purpose of this study was to determine whether lysyl oxidase inhibition using β-aminopropionitrile (BAPN) induced region-specific aortopathies in mice. The effects of BAPN were first characterized with regard to dose, strain, age, and sex. Subsequently, BAPN was administered to young male C57BL/6J mice. BAPN-induced aortic rupture predominantly occured or originated in the descending thoracic aorta. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while relatively sporadic in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissection with false lumen formation, macrophage infiltration, collagen deposition, and remodeling of the media and adventitia. Cells surrounding the false lumen were predominantly positive for α-smooth muscle actin. To investigate the molecular basis of the regional heterogeneity, ascending and descending thoracic aortas were harvested after one week of BAPN administration prior to the appearance of overt pathology. BAPN compromised contractile properties in both regions equivalently, while RNA sequencing demonstrated that BAPN altered transcriptomes related to extracellular matrix and cell division differentially between the two regions. In conclusion, BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in young mice.
Project description:Comparison of gene expression levels in ductus arteriosus (DA) and aorta in full-term (21 days) neonates of Brown-Norway (BN) and Fischer344 (F344) rats We analyzed the fold difference between BN and F344 rats in ductus arteriosus in order to identify the down-regulated and up-regulated genes specifically in BN rat's DA. The differences in aorta was also examined for additional comparison. Total RNA was extracted from aorta and DA tissues from BN and F344 rat neonates one hour after delivery, and converted to biotin-labeled cRNAs that were hybridized to Affymetrix Rat Gene 1.0 ST Array.
Project description:The ductus arteriosus constricts after birth or hatching and eventually closes to terminate embryonic circulation. Chicken embryos have two long ductus arteriosus. Then the pulmonary artery-sided and descending aorta-sided ductus arteriosus have distinct functional characteristics, such as oxygen responsiveness. We used microarrays to elucidate the difference between the pulmonary artery-sided and descending aorta-sided ductus arteriosus in their transcriptional profiles.
Project description:In order to understand the mechanisms responsible for lethal JAK2V617F-dependent aortic disease, we performed RNA sequencing in the aorta of 7-week old Jak2V617F HC-EC and control Jak2WT mice
Project description:Comparison of gene expression levels in ductus arteriosus (DA) and aorta in full-term (21 days) neonates of Brown-Norway (BN) and Fischer344 (F344) rats We analyzed the fold difference between BN and F344 rats in ductus arteriosus in order to identify the down-regulated and up-regulated genes specifically in BN rat's DA. The differences in aorta was also examined for additional comparison.
Project description:Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, revealing 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests, and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (HR = 1.43 per SD; CI 1.32-1.54; P = 3.3·10-20). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.
Project description:We report dynamic temporal and spatial smooth muscle cell phenotype modulation using aortic single cell RNA sequencing in a murine model of Marfan syndrome (Fbn1C1041G/+) and littermate controls. Aortic root/ascending aortic tissue samples from both genotypes were studied at 4 and 24 weeks of age. The non-aneurysmal descending thoracic aorta was also studied at 24 weeks. Finally human aortic tissue from a Marfan syndrome patient undergoing aneurysm repair surgery was studied.