Key Regulators of Angiogenesis and Inflammation Are Dysregulated in Patients with Varicose Veins
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ABSTRACT:
SUBMITTER: Zalewski D
PROVIDER: S-EPMC11204110 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:BackgroundSurgery on varicose veins (crossectomy and stripping) may lead to recurrence, with clinical and socioeconomic repercussions. The etiopathogenesis of varicose veins has yet to be fully understood.ObjectiveStudy the expression of endoglin and other molecules involved in the neovascularisation process in patients suffering from this disease.MethodsTotal of 43 patients that have undergone surgery for varicose veins (24 primary and 19 recurrent). Endoglin and other molecules were identified on the venous wall (proximal -saphenofemoral junction- and distal), via real-time RT-PCR, and in serum, via ELISA: endoglin (Eng), vascular endothelial growth factor (VEGF-A), its receptors 1 and 2 (VEGFR1 or FLT1), (VEGFR2 or FLK), and the hypoxia-inducible factor (HIF-1A). All the patients signed a consent form.ResultsThe recurrent group recorded a higher expression of Eng, VEGF-A, VEGFR1, and VEGFR2 at the level of proximal venous wall compared to the primary group. HIF-1A did not record any differences. As regards the determination of the distal venous wall, no markers recorded differences between the groups. Among the serum determinations, only sFLT1 recorded a significant drop among the patients with recurrent varicose veins.ConclusionsPatients with recurrent varicose veins record a higher expression of endoglin and other markers of angiogenesis in proximal veins. Endoglin in the blood (sEng) serves no apparent purpose in recurrent varicose veins.
| S-EPMC9025299 | biostudies-literature
Project description: Not available
| S-EPMC8660237 | biostudies-literature
Project description:Abdominal aortic aneurysm (AAA) is a chronic vascular disease caused by localized weakening and broadening of the abdominal aorta. AAA is a clearly underdiagnosed disease and is burdened with a high mortality rate (65-85%) from AAA rupture. Studies indicate that abnormal regulation of angiogenesis and inflammation contributes to progression and onset of this disease; however, dysregulations in the molecular pathways associated with this disease are not yet fully explained. Therefore, in our study, we aimed to identify dysregulations in the key regulators of angiogenesis and inflammation in patients with AAA in peripheral blood mononuclear cells (using qPCR) and plasma samples (using ELISA). Expression levels of ANGPT1, CXCL8, PDGFA, TGFB1, VEGFB, and VEGFC and plasma levels of TGF-alpha, TGF-beta 1, VEGF-A, and VEGF-C were found to be significantly altered in the AAA group compared to the control subjects without AAA. Associations between analyzed factors and risk factors or biochemical parameters were also explored. Any of the analyzed factors was associated with the size of the aneurysm. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors potentially involved in AAA formation, giving new insight into the molecular pathways involved in the development of this disease and providing candidates for biomarkers that could serve as diagnostic or therapeutic targets.
| S-EPMC10418409 | biostudies-literature
Project description:tRNA-derived fragments (tRFs) with a size of 15-50 nt are derived from mature or precursor tRNAs and associated with a variety of pathological conditions. However, the roles of tRFs in varicose veins (VVs) are largely unknown. The aim of this study was to identify the tRFs involved in VVs and predict their potential biological functions. We first performed small RNA-seq to investigate the expression profiles of tRFs in vascular tissue of VVs patients and healthy controls. In total, 13,789 tRFs were obtained, accounting for 4 % of the total small RNA. Moreover, 45 tRFs were remarkably changed, of which 14 were up-regulated and 31 were down-regulated. Gene Ontology analysis showed that the target genes of these differently expressed tRFs are mainly involved in transcriptional functions, DNA-template and nervous system development. Kyoto Encyclopedia of Genes and Genomes analysis revealed that target genes of these differently expressed tRFs were significantly enriched the wnt signaling pathway and the calcium signaling pathway which regulate local hypoxia and degradation of extracellular matrix(ECM) processes, which play an important role in the development of VVs. Furthermore, differentially expressed mRNA-tRF-non coding RNA regulatory network was constructed which revealed that tRFs may play a central role in this interaction network and correlate with many mRNAs and ncRNAs. Additionally, two up-regulated tRFs (tRF-36-F900BY4D84KRIME and tRF-23-87R8WP9IY) and one down-regulated tRFs (tRF-40-86J8WPMN1E8Y7Z2R)) were identified and verified. These results show that tRFs are aberrantly expressed in vascular tissue of patients with VVs and might play important roles in the development of VVs.
2020-11-06 | GSE122109 | GEO
Project description:BackgroundVaricose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease.MethodsWe applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development.ResultsMachine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% CI, 1.51-2.01; P<0.0001). A genome-wide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse-variance weighted: odds ratio, 1.26; P=2.07×10-16).ConclusionsUsing data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.
| S-EPMC6400474 | biostudies-literature
Project description:The aim of this study was to assess behavioural recovery from the patient's perspective as a prespecified secondary outcome in a multicentre parallel-group randomized clinical trial comparing ultrasound-guided foam sclerotherapy (UGFS), endovenous laser ablation (EVLA) and surgery for the treatment of primary varicose veins.Participants were recruited from 11 UK sites as part of the CLASS trial, a randomized trial of UGFS, EVLA or surgery for varicose veins. Patients were followed up 6 weeks after treatment and asked to complete the Behavioural Recovery After treatment for Varicose Veins (BRAVVO) questionnaire. This is a 15-item instrument that covers eight activity behaviours (tasks or actions an individual is capable of doing in an idealized situation) and seven participation behaviours (what the individual does in an everyday, real-world situation) that were identified to be important from the patient's perspective.A total of 798 participants were recruited. Both UGFS and EVLA resulted in a significantly quicker recovery compared with surgery for 13 of the 15 behaviours assessed. UGFS was superior to EVLA in terms of return to full-time work (hazard ratio 1·43, 95 per cent c.i. 1·11 to 1·85), looking after children (1·45, 1·04 to 2·02) and walks of short (1·48, 1·19 to 1·84) and longer (1·32, 1·05 to 1·66) duration.Both UGFS and EVLA resulted in more rapid recovery than surgery, and UGFS was superior to EVLA for one-quarter of the behaviours assessed. The BRAVVO questionnaire has the potential to provide important meaningful information to patients about their early recovery and what they may expect to be able to achieve after treatment.
| S-EPMC4819709 | biostudies-other
Project description:The aim of the present study was to perform a literature review about the symptoms, treatment and prevention of varicose veins (VV) within the occupational medicine setting. I reviewed scientific articles, books, master's and doctoral dissertations and synthesized the results of quantitative and qualitative studies. I further retrieved information from Brazilian federal government occupational health websites. The time frame considered was the period from 2004 through 2018. VV are abnormally dilated, twisted and congested veins caused by prolonged peripheral venous hypertension and chronic venous insufficiency. VV most commonly involve the lower limbs in association with static posture and continuous contraction which exhaust the muscles, especially among individuals who remain standing over long periods of time. VV are associated with risk factors such as obesity, sedentary lifestyle and hormones. Symptoms include feelings of tiredness, pain and swelling. When untreated VV might result in venous ulcers. Occupational physicians should promote changes in the workers' lifestyle, particularly as concerns physical activity (stretching and walking), local massage and elevating the lower limbs - feet about 15 cm above the heart level, and prescribe compression stockings or bandages, and medications such as diosmin, calcium dobesilate, rutosides and horse chestnut extract.
| S-EPMC7363262 | biostudies-literature
Project description: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).
| S-EPMC3908920 | biostudies-literature
Project description:To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix.
2016-05-03 | PXD002555 | Pride
Project description:IntroductionVaricose veins (VV) negatively impact quality of life (QoL) and have risks of major complications including bleeding, ulceration and phlebitis. During the COVID-19 pandemic, the VSGBI (Vascular Society of Great Britain and Ireland) and GIRFT (Get It Right First Time) classified VVs as lowest priority for intervention.ObjectiveThis study aims to determine harm caused and the impact on the QoL on patients waiting for their VVs procedures for more than 1 year.MethodsThis was a prospective study conducted at the Norfolk and Norwich University Hospital (NNUH). Patients with VVs awaiting intervention for >1 year were included in the study. Patients with CEAP C6 disease were considered to be too high risk to be invited for treatment during the Covid-19 pandemic. Patients were sent QoL questionnaires and underwent a telephone consultation to assess harm. Both generic (EQ-VAS and EQ-5D) and disease-specific (AVVQ and CIVIQ-14) instruments were utilised. There were no control groups available for comparison.Results275 patients were identified (37.1% male) with median time on waiting list of 60 weeks (IQR 56-65). 19 patients (6.9%) came to major harm, including phlebitis (3.6%), bleeding (1.8%) and ulceration (1.8%). Fifty-two patients (18.9%) had minor harm, including worsening pain (12.7%) and swelling (6.2%). 6.9% reported psychological harm. Rising CEAP stage was also associated with worsening level of harm in patients with C5-6 disease (p < 0.0001). Only 8.7% stated they would decline surgery during the pandemic. 104 QoL questionnaires were returned. Median EQ-VAS and EQ-5D was 75 (IQR: 60-85) and 0.685 (0.566-0.761), respectively. Median AVVQ score was 23.2 (14.9-31.0) and CIVIQ-14 score was 33 (21-44).ConclusionsThis study highlights the impact of delaying VVs surgery during a pandemic. A significant rate of both major and minor as well as psychological harm was reported. In addition, VVs had a significant detriment to quality of life.
| S-EPMC9713534 | biostudies-literature