Project description:The aim of this study was to assess the relative gene expression in human AAA and AOD. Genome-wide expression analysis of abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) specimens obtained from 20 patients with small AAA (mean maximum aortic diameter=54.3±2.3 mm), 29 patients with large AAA (mean maximum aortic diameter=68.4±14.3 mm), and 9 AOD patients (mean maximum aortic diameter=19.6±2.6 mm). Relative aortic gene expression was compared with that of 10 control aortic specimen of organ donors.
Project description:Analysis of differential gene expression for rutured vs stable abdominal aortic aneurysms (AAA) and for intermediate size (≤55mm) vs large (>70mm) AAA.
Project description:Abdominal aortic aneurysm (AAA) is a common degenerative cardiovascular disease without clear understanding of its pathobiology. To detect AAA associated variants that may affect gene regulation, we generated H3K27ac HiChIP data for aortic smooth muscle cells (AoSMC) and aortic endothelia cells (HAEC), the two cell types most relevant to the AAA disease. We further implemented cell type-specific REs defined from HiChIP experiments, and observed the consistency between the chromatin accessibility of REs and the expression levels of their target genes. Moreover, the cell type-specific REs contributed to detect the AAA most relevant cell type, AoSMC, and locate the important AAA-related TFs, ERG and KLF family.
Project description:Abdominal aortic aneurysm (AAA) is a permanent segmental dilatation of the abdominal aorta, contributing to a high mortality once rupture. We performed RNA-sequencing analysis of abdominal aorta tissues from 14 participants, including seven patients with AAA and seven control individuals.
Project description:Abstract: The pathogenesis of AAA involves vascular inflammation and oxidative stress. Astragali Radix contains cycloastragenol (CAG) known to have anti-inflammatory and anti-oxidative properties. We hypothesized that CAG supplement impairs AAA progression. AAA was induced in male rats by intraluminal elastase infusion in the infrarenal aorta and treated daily with CAG (125 mg/kg/day). Aortic expansion was followed weekly by ultrasound, with euthanization at day 28. Changes in AAA wall composition were analyzed at mRNA levels, histology, zymography and explorative proteomic analyses. At day 28, mean AAA diameter was 37% lower in CAG group (p<0.0001). In aneurysm cross sections, elastin content was insignificantly higher in CAG group (10.5% ± 5.9% vs 19.9% ± 16.8%, p=0.20) with more preserved elastin lamellae structures (p=0.0003) and with no microcalcifications. Aneurysmal matrix metalloprotease-2 activity was reduced by CAG treatment (p=0.022), and mRNA levels of inflammatory- and antioxidative markers showed no difference between groups. Explorative proteomic analysis showed no difference in protein levels when adjustment for multiple testing. Amongst unadjusted affected proteins were fibulin-5 (p=0.02), aquaporin-1 (p=0.02) and prostacyclin synthase (p=0.006). CAG impairs experimental AAA progression by reduction of elastin degradation through decreased MMP-2 activity, thus CAG could be considered tested in AAA patients.
Project description:The aim of this study was to assess the gene expression profile of biopsies obtained from the neck of human AAAs. Genome-wide expression analysis of AAA neck specimen obtained from 14 patients with AAA (mean maximum aortic diameter=62.6±18.0 mm). Relative aortic gene expression was compared with that of 8 control aortic specimen of organ donors.
Project description:Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving aortic rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. The transcriptional regulator PR domain–containing protein 16 (PRDM16) is highly expressed in the aorta, but its functions in the aorta are largely unknown. By RNA-seq analysis, we found that vascular smooth muscle cell–specific (VSMC-specific) Prdm16-knockout (Prdm16SMKO) mice already showed extensive changes in the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation in the abdominal aorta under normal housing conditions without any pathological stimuli. Human AAA lesions displayed lower PRDM16 expression. Periadventitial elastase application to the suprarenal region of the abdominal aorta aggravated AAA formation in Prdm16SMKO mice. During AAA development, VSMCs undergo apoptosis because of both intrinsic and environmental changes, including inflammation and ECM remodeling. Prdm16 deficiency promoted inflammation and apoptosis in VSMCs. A disintegrin and metalloproteinase 12 (ADAM12) is a gelatinase that can degrade various ECMs. We found that ADAM12 is a target of transcriptional repression by PRDM16. Adam12 knockdown reversed VSMC apoptosis induced by Prdm16 deficiency. Our study demonstrated that PRDM16 deficiency in VSMCs promoted ADAM12 expression and aggravates AAA formation, which may provide potential targets for AAA treatment.
Project description:An abdominal aortic aneurysm (AAA) is a pathological widening of the aortic wall characterized by loss of AoSMCs, extracellular matrix degradation and local inflammation. This condition is often asymptomatic until rupture occurs, leading to high morbidity and mortality rates. We conducted single-cell RNA sequencing (scRNA-seq) from AAA patients´s specimens to profile gene expression at single cell level and to gain insight on cell types relevant to disease dynamics.
