Dataset Information

BPI and KIR6.1 as significant hub genes for vein graft restenosis.

ABSTRACT: Background: Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients.

Methods: This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Gene Expression Omnibus database. A repeatability test for the GSE110398 dataset was performed using R language. This included the identification of differentially expressed genes (DEGs), enrichment analysis via Metascape software, pathway enrichment analysis, and construction of a protein-protein interaction network and a hub gene network.

Results: Twenty-four DEGs were identified between VGR and control groups. The four most important hub genes (KIR6.1, PCLP1, EDNRB, and BPI) were identified, and Pearson's correlation coefficient showed that KIR6.1 and BPI were significantly correlated with VGR. KIR6.1 could also sensitively predict VGR (0.9?
Conclusion: BPI and KIR6.1 were differentially expressed in vessels with and without stenosis after vascular transplantation, suggesting that these genes or their encoded proteins may be involved in the occurrence of VGR.

SUBMITTER: Bai YP

PROVIDER: S-EPMC7711236 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

<i>BPI</i> and <i>KIR6.1</i> as significant hub genes for vein graft restenosis.

Bai Yun-Peng YP Yao Bo-Chen BC Wang Mei M Liu Xian-Kun XK Zhu Xiao-Long XL Wang Lian-Qun LQ Jiang Nan N Guo Zhi-Gang ZG Chen Qing-Liang QL

The Journal of international medical research 20201101 11

<h4>Background</h4>Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients.<h4>Methods</h4>This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Ge ...[more]

PMID: 33259239

Similar Datasets

Project description:OBJECTIVE:Approximately 30% of autogenous vein grafts develop luminal narrowing and fail because of intimal hyperplasia or negative remodeling. We previously found that vein graft cells from patients who later develop stenosis proliferate more in vitro in response to growth factors than cells from patients who maintain patent grafts. To discover novel determinants of vein graft outcome, we have analyzed gene expression profiles of these cells using a systems biology approach to cluster the genes into modules by their coexpression patterns and to correlate the results with growth data from our prior study and with new studies of migration and matrix remodeling. METHODS:RNA from 4-hour serum- or platelet-derived growth factor (PDGF)-BB-stimulated human saphenous vein cells obtained from the outer vein wall (20 cell lines) was used for microarray analysis of gene expression, followed by weighted gene coexpression network analysis. Cell migration in microchemotaxis chambers in response to PDGF-BB and cell-mediated collagen gel contraction in response to serum were also determined. Gene function was determined using short-interfering RNA to inhibit gene expression before subjecting cells to growth or collagen gel contraction assays. These cells were derived from samples of the vein grafts obtained at surgery, and the long-term fate of these bypass grafts was known. RESULTS:Neither migration nor cell-mediated collagen gel contraction showed a correlation with graft outcome. Although 1188 and 1340 genes were differentially expressed in response to treatment with serum and PDGF, respectively, no single gene was differentially expressed in cells isolated from patients whose grafts stenosed compared with those that remained patent. Network analysis revealed four unique groups of genes, which we term modules, associated with PDGF responses, and 20 unique modules associated with serum responses. The "yellow" and "skyblue" modules, from PDGF and serum analyses, respectively, correlated with later graft stenosis (P = .005 and P = .02, respectively). In response to PDGF, yellow was also associated with increased cell growth. For serum, skyblue was also associated with inhibition of collagen gel contraction. The hub genes for yellow and skyblue (ie, the gene most connected to other genes in the module), scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN), respectively, were tested for effects on proliferation and collagen contraction. Knockdown of SCARA5 increased proliferation by 29.9% ± 7.8% (P < .01), whereas knockdown of SBSN had no effect. Knockdown of SBSN increased collagen gel contraction by 24.2% ± 8.6% (P < .05), whereas knockdown of SCARA5 had no effect. CONCLUSIONS:Using weighted gene coexpression network analysis of cultured vein graft cell gene expression, we have discovered two small gene modules, which comprise 42 genes, that are associated with vein graft failure. Further experiments are needed to delineate the venous cells that express these genes in vivo and the roles these genes play in vein graft healing, starting with the module hub genes SCARA5 and SBSN, which have been shown to have modest effects on cell proliferation or collagen gel contraction.

Project description:BackgroundThe prevalence of coronary artery disease is increasing. As a common treatment method, coronary artery bypass transplantation surgery can improve heart problems while also causing corresponding complications. Venous graft restenosis is one of the most critical and intractable complications. Stem cell-derived exosomes could have therapeutic promise and value. However, as exosomes alone are prone to inactivation and easy removal, this therapeutic method has not been widely used in clinical practice. Methacrylated gelatin (GelMA) is a polymer with a loose porous structure that maintains the biological activity of the exosome and can control its slow release in vivo. In this study, we combined human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and GelMA to explore their effects and underlying mechanisms in inhibiting venous graft restenosis.ResultsHuman umbilical cord mesenchymal stem cells (hUCMSCs) were appraised using flow cytometry. hUCMSC-Exos were evaluated via transmission electron microscopy and western blotting. hUCMSC-Exos embedded in a photosensitive GelMA hydrogel (GelMA-Exos) were applied topically around venous grafts in a rat model of cervical arteriovenous transplantation, and their effects on graft reendothelialization and restenosis were evaluated through ultrasonic, histological, and immunofluorescence examinations. Additionally, we analyzed the material properties, cellular reactions, and biocompatibility of the hydrogels. We further demonstrated that the topical application of GelMA-Exos could accelerate reendothelialization after autologous vein transplantation and reduce restenosis in the rat model. Notably, GelMA-Exos caused neither damage to major organs in mice nor excessive immune rejection. The uptake of GelMA-Exos by endothelial cells stimulated cell proliferation and migration in vitro. A bioinformatic analysis of existing databases revealed that various cell proliferation and apoptosis pathways, including the mammalian target of rapamycin (mTOR)-phosphoinositide 3-kinase (PI3K)-AKT signaling pathways, might participate in the underlying regulatory mechanism.ConclusionsCompared with the tail vein injection of hUCMSC-Exos, the local application of a mixture of hUCMSC-Exos and GelMA was more effective in promoting endothelial repair of the vein graft and inhibiting restenosis. Therefore, the proposed biomaterial-based therapeutic approach is a promising treatment for venous graft restenosis.

Dataset Information

BPI and KIR6.1 as significant hub genes for vein graft restenosis.

Publications

<i>BPI</i> and <i>KIR6.1</i> as significant hub genes for vein graft restenosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets