Fractalkine Antibody Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mice model
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PROVIDER: PRJNA678708 | ENA |
REPOSITORIES: ENA
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Project description:Fractalkine Antibody Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mice model
2021-09-15 | GSE161555 | GEO
Project description:1α,25-Dihydroxyvitamin D3 encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous Fistulas
2021-04-07 | GSE161554 | GEO
Project description:In patients with severe kidney disease AVF are surgically placed in order to create good access for hemodialysis. In these dialysis patients the failure rates of AVF can be as high as 24% within 6 months after surgery, causing ineffective dialysis and necessitating additional clinical interventions. The pathological processes known to lead to AVF failure are beginning to be unravelled include the formation of venous neointimal hyperplasia (VNIH), thrombosis (Chang et al. PMID 16105066), and venous stenosis (Kanterman et al. PMID7892454, Tang et al. 1998), resulting in a reduced blood flow through the fistula. We established a rat model for AVF failure in human kidney dialysis patients. The characterization of this model has been previously described (Globerman et al. 2011, PubmedID:22002501). In this model the AVFs are surgically constructed in the right leg by connecting the superficial epigastric vein SEV to the common femoral artery (CFA), resulting in exposure of the SEV to arterial pressure with pulsatile and low resistant flow patterns (Globerman et al. 2011, PMID22002501). In the present study we utilized this AVF model in order to assess the effects of arterialized flow, with consequent pathological changes of the vessel wall due to surgical AVF instalment, on the transcriptome of endothelium from the SEV. Within the SEV these pathologies of the vessel wall include the formation of NIH in the main branch, and stenosis in the side branches. By employing this rat model we assessed the changes of the endothelial transcriptome in relation to these pathologies in order to gain mechanistic understanding of the potential roles of venous endothelium in AVF failure, as well as to identify potential biomarkers preceding AVF failure. AVF surgery was performed on N=6 rats, and 13-14 days after surgery the rats were sacrificed. AVFs were extracted from the rats, and microarray transcriptome analyses were performed on luminal endothelial cells that isolated from four different sites of the AVF by employing Laser Capture Microdissection (LCM). These sites included (i) N=5 AVF sections of the superficial epigastric vein (SEV) with neointimal hyperplasia (NIH), (ii) N=3 AVF sections of SEV side branches with luminal stenosis, (iii), N=6 sections of the SEV located distally from a ligation thereby omitting exposure to arterialized flow and consequently preventing the development of NIH or stenosis, and (iv) N=3 sections of the AVF common femoral artery without signs of NIH or stenosis.
2013-10-01 | E-GEOD-46126 | biostudies-arrayexpress
Project description:In patients with severe kidney disease AVF are surgically placed in order to create good access for hemodialysis. In these dialysis patients the failure rates of AVF can be as high as 24% within 6 months after surgery, causing ineffective dialysis and necessitating additional clinical interventions. The pathological processes known to lead to AVF failure are beginning to be unravelled include the formation of venous neointimal hyperplasia (VNIH), thrombosis (Chang et al. PMID 16105066), and venous stenosis (Kanterman et al. PMID7892454, Tang et al. 1998), resulting in a reduced blood flow through the fistula. We established a rat model for AVF failure in human kidney dialysis patients. The characterization of this model has been previously described (Globerman et al. 2011, PubmedID:22002501). In this model the AVFs are surgically constructed in the right leg by connecting the superficial epigastric vein SEV to the common femoral artery (CFA), resulting in exposure of the SEV to arterial pressure with pulsatile and low resistant flow patterns (Globerman et al. 2011, PMID22002501). In the present study we utilized this AVF model in order to assess the effects of arterialized flow, with consequent pathological changes of the vessel wall due to surgical AVF instalment, on the transcriptome of endothelium from the SEV. Within the SEV these pathologies of the vessel wall include the formation of NIH in the main branch, and stenosis in the side branches. By employing this rat model we assessed the changes of the endothelial transcriptome in relation to these pathologies in order to gain mechanistic understanding of the potential roles of venous endothelium in AVF failure, as well as to identify potential biomarkers preceding AVF failure.
2013-10-01 | GSE46126 | GEO
Project description:1α,25-Dihydroxyvitamin D3 encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous Fistulas
| PRJNA678705 | ENA
Project description:Background: Although clinical outcome of arteriovenous fistula (AVF) as a preferred vascular access for hemodialysis has been inadequate, biological mechanisms of AVF maturation and failure is still poorly understood. Since our mouse AVF model recapitulates human AVF maturation and partial failure, we hypothesized that high throughput RNA sequencing (RNA-seq) analysis would identify early changes in gene expression that might predict AVF maturation and failure. Method: Aortocaval fistula creation (AVF group) or sham operation (sham group) was performed with C57BL/6 mice (10 wk). Ultrasound was performed to confirm the AVF patency and to measure hemodynamics. Venous limbs were collected on postoperative day 7 and total RNA was extracted. After Poly-A mRNA libraries were constructed, RNA-seq was performed. Differentially expressed genes (DEG) were identified, and subsequent enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed with bioinformatics techniques. Results: 1057 DEG were identified between the AVF and sham groups. Genes in metabolic pathways were significantly downregulated in the AVF. Since gene expression patterns among the AVF group were significantly heterogenous, the AVF group was divided into 2 groups (‘normal’ AVF group; nAVF and ‘outliers’ group; OUT), and subgroup analyses were performed. Although physiological data of body weight change and hemodynamics were not different between the nAVF and OUT groups, 413 DEG were identified between them. Enrichment analyses showed significant overrepresentation of metabolism, immunity, and coagulation in the OUT group. Comparing the nAVF group with the sham group, 403 DEG were identified. Enrichment analyses showed increase of gene expression related to cell cycle, extracellular matrix, and immunity. Comparing these results with previously published data, the gene expression patterns of the nAVF group was consistent with AVF maturation and adaptive remodeling, whereas the OUT group showed attenuated difference, suggesting the heterogeneity of the AVF group reflects early gene expression changes in the process of AVF maturation and failure. Significant sex differences were not observed in the AVF group. Conclusions: A small subset of AVF undergoes aberrant biological processes in the early phase including diminished ECM remodeling, activated coagulation and upregulated metabolism, that could lead to fistula failure. Detection of these processes might be a viable translational strategy to predict fistula failure and reduce patient morbidity.
2023-10-04 | GSE244317 | GEO
Project description:Background: Clinical failure of arteriovenous fistulae (AVF) is frequently due to juxta-anastomotic neointimal hyperplasia (JANIH). Although the mouse AVF model recapitulates human AVF maturation, previous studies focused on the outflow vein distal to the anastomosis. We hypothesized that the juxta-anastomotic area (JAA) has increased NIH compared to the outflow vein. Method: AVF were created in C57BL/6 mice without or with chronic kidney disease (CKD). Temporal and spatial changes of the JAA were examined using histology and immunofluorescence. Computational techniques were used to model the AVF. RNA-seq and bioinformatic analyses were performed to compare the JAA with the outflow vein. The jugular vein to carotid artery AVF model was created in Wistar rats. Result: The neointima in the JAA shows increased volume compared to the outflow vein. Computational modeling shows increased volume of disturbed flow at the JAA compared to the outflow vein. Endothelial cells are immediately lost from the wall contralateral to the fistula exit, followed by thrombus formation and JANIH. Gene Ontology (GO) enrichment analysis of the 1862 differentially expressed genes (DEG) between the JANIH and the outflow vein identified 525 overexpressed genes. The rat jugular vein to carotid artery AVF showed changes similar to the mouse AVF. Conclusion: Disturbed flow through the JAA correlates with rapid endothelial cell loss, thrombus formation, and JANIH; late endothelialization of the JAA channel correlates with late AVF patency. Early thrombus formation in the JAA may influence later development of JANIH.
2023-12-08 | GSE249267 | GEO
Project description:This study characterized the coordinated molecular changes evoked in the structure and composition of the wall of a venous segment exposed to high fistula flow.
2015-07-17 | GSE39488 | GEO
Project description:The cellular evolutions and molecular programs underlying the arteriovenous fate settling of embryonic vascular endothelial cells (ECs) are critical for understanding arteriogenesis and inspiring new approaches for regenerative biology. Using different strategies of single-cell RNA sequencing, we constructed the transcriptional landscape of early arteriovenous EC development in both mouse and human embryos, demonstrating the evolutionary conservation of principal vascular EC types and providing a series of conserved arteriovenous genes. We showed an unexpected diversity of arteriovenous characteristics in morphologically alike vascular plexus and further uncovered two transcriptomically distinct arterial EC types, whereas most of heterologous ligand-receptor pairs were shared by different arterial vasculatures. By computational predicting and further genetic lineage tracing, we revealed the widespread venous arterialization in the mid-gestational mouse embryo proper. Interestingly, we demonstrated at transcriptomic level that Notch1 was dispensable for venous arterialization but required subsequently for the arterial feature strengthening in the arterial plexus ECs. Altogether, our findings unprecedentedly detail the comprehensive single-cell mapping of early embryonic vascular ECs in vivo, decipher an asymmetric arteriovenous characteristics different than that in adults, and reveal an extensive venous-to-arterial fate conversion in the vascular plexus.
2022-01-26 | GSE94877 | GEO
Project description:Transcriptome characterization of venous endothelium during the formation of neointimal hyperplasia and stenosis in a rat arteriovenous fistula model for kidney dialysis
| PRJNA197335 | ENA