Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Aortic smooth muscle cell phenotype modulation during Marfan syndrome aneurysm formation

ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE153534 | GEO | 2020/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Smooth muscle cell-specific Klf4 deletion in Marfan syndrome aortic root aneurysm

Project description:Aortic smooth muscle cell (SMC) phenotype modulation is a central feature of cell-mediated pathology in Marfan syndrome aortic aneurysm and Klf4 is proposed to contribute to this process. We generated mice with smooth muscle cell-specific Klf4 deletion using an Myh11-creERT2 transgene, induced deletion at 8 weeks and performed single cell RNA sequencing at 24 weeks on whole aortic root tissues.

2022-08-23 | GSE206227 | GEO

17 -estradiol impedes aortic root dilation and rupture in male Marfan mice

Project description:Thoracic aortic aneurysms have a higher prevalence in male patients compared to female patients. Marfan syndrome causes a hereditary form of TAA with dilation of the aortic root. Male patients with Marfan syndrome are more likely than women to have aortic dilation and dissection and mouse models of Marfan syndrome demonstrate larger aortic roots in males compared to females even after adjustment for body size. Similar sex disparities are present in patients and models of abdominal aortic aneurysms where estrogen has been demonstrated to attenuate aneurysm formation perhaps through anti-inflammatory mechanisms. In this study we demonstrate the effects of estrogen on aortic dilation and rupture in a Marfan mouse model and we investigate if these effects operate through suppression of complement components of the immune system.

2024-02-14 | PXD037853 | Pride

A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

Project description:Background: Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. Results: We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. Conclusions: Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 x 10-6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater. Keywords: disease state comparison; Marfan syndrome; cultured skin fibroblasts

2007-09-14 | GSE8759 | GEO

Understanding the role of TGFbeta signaling on aortic aneurysm and rupture using Marfan syndrome mouse models

Project description:Although abnormal TGFbeta signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, the precise role of TGFbeta signaling in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to investigate the role of TGFbeta signaling in molecular pathways of pathogenesis associated with development of aortic aneurysm and aortic rupture. This study reports an isoform-specific effect of TGFbeta in MFS aortic disease and the effects of deleting the first hybrid domain of fibrillin-1 on TGFbeta signaling. Distinct molecular differences in mouse models of aneurysm (Fbn_GT-8_plus), of aneurysm and rupture (Fbn1_GT-8_H1delta), and of microdissection (Fbn1_H1delta_plus) were identified, which associated with TGFbeta signaling and extracellular matrix composition, possibly contributing to the development of dissection and rupture. These findings offer new insights into the pathophysiological mechanisms that potentially drive initiation of aortic dissection and could pave the way for development of new treatment targets of aortic disease.

2023-10-09 | PXD036222 | Pride

Dissecting aortic aneurysm in Marfan syndrome is associated with losartan-sensitive transcriptomic modulation of aortic cells

Project description:To improve our limited understanding of the pathogenesis of thoracic aortic aneurysm (TAA) leading to acute aortic dissection, we used single-cell RNA sequencing to profile disease-relevant transcriptomic changes of aortic cell populations in a well-characterized mouse model of the most commonly diagnosed form of Marfan syndrome (MFS). As result,MFSmod were identified only in the aorta of Fbn1mgR/mgR mice. In situ hybridizations of diagnostic transcripts located MFSmod cells to the intima of Fbn1mgR/mgR aortas. Consistent with angiotensin II type I receptor (At1r) contribution to TAA development, MFSmod cells were absent in the aorta of Fbn1mgR/mgR mice treated with the At1r antagonist losartan. Altogether, our findings indicate that a discrete dynamic alteration of aortic cell identity is associated with dissecting TAA in MFS mice and increased risk of aortic dissection in MFS patients.

2023-06-27 | GSE227776 | GEO

Aortic smooth muscle cell phenotype modulation during Marfan syndrome aneurysm formation

Project description:Aortic smooth muscle cell phenotype modulation during Marfan syndrome aneurysm formation

| PRJNA642963 | ENA

Ang II type 1a receptor in Marfan syndrome

Project description:Using Cdh5-Cre and Sm22-Cre transgenes to characterize the impact of disruption of the angiotensin II type 1a receptor (AT1ar) in vascular endothelial and smooth muscle cells, respectively, of wild type (WT) mice compared to fibrillin-1 hypomorphic mice (Fbn1mgR/mgR mice) that replicate early onset progressively severe Marfan syndrome (MFS) with dissecting thoracic aortic aneurysm (TAA).

2018-01-30 | GSE109797 | GEO

Transcription profiling of human patients with aortic aneurysms associated with tricuspid and bicuspid valves

Project description:Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA. Experiment Overall Design: Aneurysmal tissue of ascending aorta was collected from 13 patients with bicuspid aortic valve (BAV) and 12 patients with tricuspid aortic valve (TAV). Patients were selected on the basis of aortic diameter, age and other disease conditions. Patients with giant cell aortitis, cardiovascular abnormalities, inherited connective tissue disorders such as Marfan and Ehlers-Danlos syndrome were excluded from the study. RNA was extracted using Invitrogen RNA extraction kit and shown to be of adequate quality before application to Affymetrix microarray U133A gene chips probing for over 16,000 genes per chip. Two different methods of data analysis were performed: a linear model and GeneSpring.

2009-02-07 | E-GEOD-5180 | biostudies-arrayexpress

Marfan syndrome rats

Project description:Marfan syndrome rat aorta

| PRJEB33334 | ENA

Marfan syndrome in mice

Project description:Marfan syndrome in mice

| PRJNA431794 | ENA