PCSK9 promotes vein graft lesion development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA862083 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20627564.fastq.gz | Fastqsanger.gz | |||
| SRR20627565.fastq.gz | Fastqsanger.gz | |||
| SRR20627566.fastq.gz | Fastqsanger.gz | |||
| SRR20627567.fastq.gz | Fastqsanger.gz | |||
| SRR20627568.fastq.gz | Fastqsanger.gz |
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Project description:To explore a novel mechanism of macrophage activation and vein graft disease induced by circulating PCSK9 in an LDLR-independent fashion
2023-03-30 | GSE209669 | GEO
Project description:Occlusive artery disease (CAD) is the leading cause of death worldwide. Bypass graft surgery remains the prevalently performed treatments for occlusive arterial disease, and veins are the most frequently used conduits for surgical revascularization. However, clinical efficacy is highly affected by the long-term potency rates of vein grafts, and no optimal treatments are available for prevention of vein graft restenosis (VGR) until today. Therefore, it is urgent to improve the understanding of molecular mechanisms involved in mediating VGR, and thereby provide potential potent therapeutic targets for prevention of vein graft failure. In this study, we aim to explore potential crucial genes and pathways associated with VGR and provide valid biological information for further investigation of VGR.
2018-05-23 | GSE110398 | GEO
Project description:Gene expression profiling of vein graft restenosis
| PRJNA433625 | ENA
Project description:To further development of our gene expression approach to cardiovascular disease, we have employed microarray expression profiling as a discovery platform to identify genes with the potential to distinguish the therapeutic target of the vein graft restenosis following coronary artery bypass grafting. Vein graft samples were obtained from model rats which received external jugular vein-carotid bypass grafting at different postoperative timepoints (n=3/group; day 7, 14 and 28, respectively). Vein samples were also obtained from control rats without vascular grafting (n=3/group; day 0). Time-dependent gene expression profiles were described with microarray analysis. Expression of three lncRNA-mRNA pairs (AF062402-Src, BC091437-Edg1 and BC166461- Mcam) from this signature were quantified in the same RNA samples by real-time PCR, confirming the accuracy of the microarray data.
2020-06-16 | GSE152538 | GEO
Project description:Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. While previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on VGF. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing (snRNA-seq) and spatial transcriptomics (ST) analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-cartoid vein bypass implantation in a canine model (n=4). Collectively, we find that vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies.
2024-05-29 | GSE263281 | GEO
Project description:Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. While previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on VGF. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing (snRNA-seq) and spatial transcriptomics (ST) analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-cartoid vein bypass implantation in a canine model (n=4). Collectively, we find that vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies.
2024-05-29 | GSE263280 | GEO
Project description:ObjectiveDespite its large clinical impact, the underlying mechanisms for vein graft failure remain obscure and no effective therapeutic solutions are available. We tested the hypothesis that Notch signaling promotes vein graft disease.Approach and resultsWe used 2 biotherapeutics for Delta-like ligand 4 (Dll4), a Notch ligand: (1) blocking antibody and (2) macrophage- or endothelial cell (EC)-targeted small-interfering RNA. Dll4 antibody administration for 28 days inhibited vein graft lesion development in low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice, and suppressed macrophage accumulation and macrophage expression of proinflammatory M1 genes. Dll4 antibody treatment for 7 days after grafting also reduced macrophage burden at day 28. Dll4 silencing via macrophage-targeted lipid nanoparticles reduced lesion development and macrophage accumulation, whereas EC-targeted Dll4 small-interfering RNA produced no effects. Gain-of-function and loss-of-function studies suggested in vitro that Dll4 induces proinflammatory molecules in macrophages. Macrophage Dll4 also stimulated smooth muscle cell proliferation and migration and suppressed their differentiation.ConclusionsThese results suggest that macrophage Dll4 promotes lesion development in vein grafts via macrophage activation and crosstalk between macrophages and smooth muscle cells, supporting the Dll4-Notch axis as a novel therapeutic target.
| S-EPMC5003117 | biostudies-literature
Project description:Development of gene expression signatures for vein graft restenosis following vascular grafting
| PRJNA639605 | ENA
Project description:We have transfected Hep2G cells with the gain-of-function mutant D374Y-PCSK9.
2008-01-30 | E-MEXP-1235 | biostudies-arrayexpress
Project description:To further understand the mechanism approach to occlusive vein grafts, we have employed RNA-seq to identify key genes in occlusive venin grafts following CABG in human. The occluded vein graft and intraoperative spare great saphenous vein of patients undergoing clinical re-coronary artery bypass grafting were obtained for RNA-seq. The sequencing results were cleaned and bioinformatics annlysis was conducted by using WGCNA and a variety of online databases and software. The key genes or proteins affecting the occurrence of vein graft restenosis were screened out(ITGB2), and the expression level of the target genes or proteins was verified by real-time PCR and Western blot. And to further learn the effect of ITGB2 in human primary venous smooth muscle cells, ITGB2 gene was silenced by SiRNA. The effect of ITGB2 silencing on proliferation, migration and invasion of venous smooth muscle cells after PDGF-BB-stimulation were detected by Edu assay, scrathch experiment and transwell experiment. And Edu assay showed that ITGB2 silencing could inhibit the proliferation of PDGF-BB sitmulated smooth muscle cells. Scratch assay showed that ITGB2 silencing inhibited the migration of PDGF-BB stimulated smooth muscle cells. Transwell assay showed that ITGB2 silencing significantly inhibited the invasion of PDGF-BB stimulated smooth muscle cells. It is indicated that ITGB2 was the key gene in vein graft restenosis,and may be the potential treatment target in restenosis patients.
2024-01-17 | GSE241205 | GEO