Dataset Information

Aberrantly expressed lncRNAs in primary varicose great saphenous veins.

ABSTRACT: Long non-coding RNAs (lncRNAs) are key regulatory molecules involved in a variety of biological processes and human diseases. However, the pathological effects of lncRNAs on primary varicose great saphenous veins (GSVs) remain unclear. The purpose of the present study was to identify aberrantly expressed lncRNAs involved in the prevalence of GSV varicosities and predict their potential functions. Using microarray with 33,045 lncRNA and 30,215 mRNA probes, 557 lncRNAs and 980 mRNAs that differed significantly in expression between the varicose great saphenous veins and control veins were identified in six pairs of samples. These lncRNAs were sub-grouped and mRNAs expressed at different levels were clustered into several pathways with six focused on metabolic pathways. Quantitative real-time PCR replication of nine lncRNAs was performed in 32 subjects, validating six lncRNAs (AF119885, AK021444, NR_027830, G36810, NR_027927, uc.345-). A coding-non-coding gene co-expression network revealed that four of these six lncRNAs may be correlated with 11 mRNAs and pathway analysis revealed that they may be correlated with another 8 mRNAs associated with metabolic pathways. In conclusion, aberrantly expressed lncRNAs for GSV varicosities were here systematically screened and validated and their functions were predicted. These findings provide novel insight into the physiology of lncRNAs and the pathogenesis of varicose veins for further investigation. These aberrantly expressed lncRNAs may serve as new therapeutic targets for varicose veins. The Human Ethnics Committee of Shanghai East Hospital, Tongji University School of Medicine approved the study (NO.: 2011-DF-53).

SUBMITTER: Li X

PROVIDER: S-EPMC3908920 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Aberrantly expressed lncRNAs in primary varicose great saphenous veins.

Li Xiang X Jiang Xiao-Yan XY Ge Jin J Wang Jing J Chen Guo-Jun GJ Xu Liang L Xie Duan-Yang DY Yuan Tian-You TY Zhang Da-Sheng DS Zhang Hong H Chen Yi-Han YH

PloS one 20140131 1

Long non-coding RNAs (lncRNAs) are key regulatory molecules involved in a variety of biological processes and human diseases. However, the pathological effects of lncRNAs on primary varicose great saphenous veins (GSVs) remain unclear. The purpose of the present study was to identify aberrantly expressed lncRNAs involved in the prevalence of GSV varicosities and predict their potential functions. Using microarray with 33,045 lncRNA and 30,215 mRNA probes, 557 lncRNAs and 980 mRNAs that differed ...[more]

PMID: 24497937

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Project description:BackgroundThe great saphenous vein (GSV) is the most commonly used conduit for coronary arterial bypass graft. However, the status of the GSV, including metabolic dysfunction such as diabetes mellitus (DM) complication, is strongly associated with vein graft failure (VGF). To date, the molecular mechanism underlying VGF remains elusive. Detailed characterization of the cellular components and corresponding expression regulation in GSVs would be of great importance for clinical decision making to reduce VGF.MethodsTo this end, we performed single-cell RNA sequencing to delineate cellular heterogeneity in three human GSV samples.ResultsScrutinization of cellular composition and expression revealed cell diversity in human GSVs, particularly endothelial cells (ECs). Our results unraveled that functional adaptation drove great expression differences between venous ECs and valvular ECs. For instance, cell surface receptor ACKR1 demarcated venous Ecs, whereas ACRK3/ACKR4 were exclusively expressed by valvular ECs. Differential gene expression analysis suggested that genes highly expressed in venous ECs were mainly involved in vasculature development and regulation of leukocyte adhesion, whereas valvular ECs have more pronounced expression of genes participating in extracellular matrix organization, ossification and platelet degranulation. Of note, pseudo-time trajectory analysis provided in silico evidence indicating that venous ECs, valvular ECs and lymphatic vessels were developmentally connected. Further, valvular ECs might be an importance source for lymphatic vessel differentiation in adults. Additionally, we found a venous EC subset highly expressing IL6, which might be associated with undesirable prognosis. Meanwhile, we identified a population of ANGPTL7+ fibroblasts (FBs), which may be profibrotic and involved in insulin resistance in human GSVs. Additionally, our data suggest that immune cells only accounted for a small fraction, most of which were macrophages. By assessing the intertwined remodeling in metabolic dysfunction that potentially increases the gene expression regulatory network in mural cells and leukocytes, we found that transcription factor KLF9 likely operated a proinflammatory program, inducing the transcription of metallothionein proteins in two mural cell subsets and proinflammatory immune cells. Lastly, cellular communication analysis revealed that proinflammatory signaling, including TRAIL, PVR, CSF and GDF, were uniquely activated in patients with metabolic dysfunction.ConclusionsOur results identified critical cell-specific responses and cellular interactions in GSVs. Beyond serving as a repertoire, this work illustrates multifactorial likelihood of VGF.

Project description:Three-dimensional computed tomography venography is a useful tool to identify increased saphenous vein diameter and provides a complementary road map for surgery in patients with varicose veins. In this study, we investigated the correlation between saphenous vein diameter on computed tomography venography and venous reflux detected on duplex ultraonography. We enrolled 152 patients (213 extremities) who underwent endovenous laser ablation therapy, following high ligation of the saphenofemoral junction between January 2014 and December 2019. All patients underwent preoperative computed tomography venography evaluation. The saphenous vein diameter was measured on computed tomography venography, and venous reflux was evaluated in the operating room using Doppler ultrasonography. Among the 152 patients included in the study, 61 showed varicose veins affecting the bilateral extremities. Among the 213 extremities investigated, 165 (77.5%) and 48 (22.5%) extremities showed varicosities involving the greater and lesser saphenous veins, respectively. Among all extremities, venous reflux was detected in 172 (80.8%). The mean diameter of the greater saphenous vein measured 5 cm distal to the saphenofemoral junction was 8.07±1.82 mm in patients with reflux and 5.11±1.20 mm in patients without reflux (p < .05). The small saphenous vein diameter measured 5 cm distal to the saphenopopliteal junction was 7.65±1.74 mm in patients with reflux and 5.04±1.80 mm in patients without reflux (p < .05). Based on the receiver operating characteristic curve, the greater saphenous vein threshold diameter of 5.880 mm measured 5 cm distal to the saphenofemoral junction was the optimal cut-off value to predict reflux (sensitivity 91.4%, specificity 81.8%). The lesser saphenous vein diameter of 5.285 mm measured 5 cm distal to the saphenopopliteal junction was the optimal cut-off value to predict reflux (sensitivity 94.9%, specificity 75.0%). Vein diameter cannot be used as an absolute reference for venous reflux; however, it may have predictive value in patients with varicose veins. Computed tomography venography based measurements of vein diameter may serve as a useful diagnostic tool to predict venous reflux and recommend treatment.

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Aberrantly expressed lncRNAs in primary varicose great saphenous veins.

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Aberrantly expressed lncRNAs in primary varicose great saphenous veins.

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