{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:59:34Z","timestamp":1781877574957,"version":"3.54.5"},"reference-count":93,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T00:00:00Z","timestamp":1587772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Uniwersytet Medyczny w Lublinie","doi-asserted-by":"publisher","award":["DS43"],"award-info":[{"award-number":["DS43"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.<\/jats:p>","DOI":"10.3390\/jcm9051251","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T01:29:15Z","timestamp":1588123755000},"page":"1251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-2009","authenticated-orcid":false,"given":"Daniel P.","family":"Zalewski","sequence":"first","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol P.","family":"Ruszel","sequence":"additional","affiliation":[{"name":"Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwi\u0142\u0142owska St., 20-080 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"St\u0119pniewski","sequence":"additional","affiliation":[{"name":"Ecotech Complex Analytical and Programme Centre for Advanced Environmentally Friendly Technologies, University of Marie Curie-Sk\u0142odowska, 39 G\u0142\u0119boka St., 20-612 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Ga\u0142kowski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, New Brunswick, NJ 08903-0019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8683-545X","authenticated-orcid":false,"given":"Jacek","family":"Bogucki","sequence":"additional","affiliation":[{"name":"Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwi\u0142\u0142owska St., 20-080 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Komsta","sequence":"additional","affiliation":[{"name":"Chair and Department of Medicinal Chemistry, Medical University of Lublin, 4 Jaczewskiego St., 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-0860","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Ko\u0142odziej","sequence":"additional","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Chmiel","sequence":"additional","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Zubilewicz","sequence":"additional","affiliation":[{"name":"Chair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Feldo","sequence":"additional","affiliation":[{"name":"Chair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9541-6353","authenticated-orcid":false,"given":"Janusz","family":"Kocki","sequence":"additional","affiliation":[{"name":"Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwi\u0142\u0142owska St., 20-080 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bogucka-Kocka","sequence":"additional","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,25]]},"reference":[{"key":"ref_1","first-page":"105","article-title":"VCP Coordinators. Epidemiology of chronic venous disorders in geographically diverse populations: Results from the Vein Consult Program","volume":"31","author":"Rabe","year":"2012","journal-title":"Int. Angiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1177\/0003319718759834","article-title":"An epidemiological survey of venous disease among general practitioner attendees in different geographical regions on the globe: The final results of the Vein Consult Program","volume":"69","author":"Vuylsteke","year":"2018","journal-title":"Angiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.jvs.2008.09.014","article-title":"Updated terminology of chronic venous disorders: The vein term transatlantic interdisciplinary consensus document","volume":"49","author":"Eklof","year":"2009","journal-title":"J. Vasc. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1258\/phleb.2012.012s19","article-title":"Clinical, aetiological, anatomical and pathological classification (CEAP): Gold standard and limits","volume":"27","author":"Rabe","year":"2012","journal-title":"Phlebology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1161\/CIRCULATIONAHA.113.006898","article-title":"Chronic venous insufficiency","volume":"130","author":"Eberhardt","year":"2014","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jvsv.2019.12.075","article-title":"CEAP classification system and reporting standard, revision 2020","volume":"8","author":"Lurie","year":"2020","journal-title":"J. Vasc. Surg. Venous Lymphat. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1056\/NEJMra055289","article-title":"Chronic venous disease","volume":"355","author":"Bergan","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4S","DOI":"10.1016\/j.jvs.2007.09.043","article-title":"The hemodynamics and diagnosis of venous disease","volume":"46","author":"Meissner","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ligi, D., Croce, L., and Mannello, F. (2018). Chronic venous disorders: The dangerous, the good, and the diverse. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092544"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.avsg.2007.03.011","article-title":"Molecular mechanisms in chronic venous insufficiency","volume":"21","author":"Bergan","year":"2007","journal-title":"Ann. Vasc. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13221-014-0024-5","article-title":"Cellular and molecular basis of venous insufficiency","volume":"6","author":"Pocock","year":"2014","journal-title":"Vasc. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mansilha, A., and Sousa, J. (2018). Pathophysiological mechanisms of chronic venous disease and implications for venoactive drug therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061669"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Serralheiro, P., Novais, A., Cairr\u00e3o, E., Maia, C., Costa Almeida, C.M., and Verde, I. (2018). Variability of MMP\/TIMP and TGF-\u03b21 receptors throughout the clinical progression of chronic venous disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010006"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/HNP.0000000000000072","article-title":"Quality of life in patients with venous stasis ulcers and others with advanced venous insufficiency","volume":"29","author":"Tracz","year":"2015","journal-title":"Holist Nurs. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1177\/1708538116685945","article-title":"Effect of socio-demographic characteristics and clinical findings on the quality of life of patients with chronic venous insufficiency","volume":"25","author":"Soydan","year":"2017","journal-title":"Vascular"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.ejvs.2015.02.007","article-title":"Editor\u2019s Choice\u2014Management of chronic venous disease: Clinical practice guidelines of the European Society for Vascular Surgery (ESVS)","volume":"49","author":"Wittens","year":"2015","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Attaran, R.R. (2018). Latest innovations in the treatment of venous disease. J. Clin. Med., 7.","DOI":"10.3390\/jcm7040077"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nrg2504","article-title":"Small silencing RNAs: An expanding universe","volume":"10","author":"Ghildiyal","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1038\/ng.3694","article-title":"General rules for functional microRNA targeting","volume":"48","author":"Kim","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nature09267","article-title":"Mammalian microRNAs predominantly act to decrease target mRNA levels","volume":"466","author":"Guo","year":"2010","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/ng.905","article-title":"MicroRNAs can generate thresholds in target gene expression","volume":"43","author":"Mukherji","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.3390\/jcm4081651","article-title":"MicroRNA Processing and Human Cancer","volume":"4","author":"Ohtsuka","year":"2015","journal-title":"J. Clin. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Inamura, K., and Ishikawa, Y. (2016). MicroRNA in lung cancer: novel biomarkers and potential tools for treatment. J. Clin. Med., 5.","DOI":"10.3390\/jcm5030036"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/FJC.0b013e318203759b","article-title":"MicroRNAs in vascular disease","volume":"57","author":"Qin","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/MOH.0000000000000424","article-title":"MicroRNAs in endothelial cell homeostasis and vascular disease","volume":"25","year":"2018","journal-title":"Curr. Opin. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1515\/cclm-2016-0576","article-title":"MicroRNAs in cardiovascular disease\u2014Clinical application","volume":"55","author":"Schulte","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1161\/CIRCRESAHA.115.306300","article-title":"MicroRNA regulation of atherosclerosis","volume":"118","author":"Feinberg","year":"2016","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/aps.2018.30","article-title":"miRNAS in cardiovascular diseases: Potential biomarkers, therapeutic targets and challenges","volume":"39","author":"Zhou","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.3389\/fgene.2019.01200","article-title":"Dysregulation of microRNA regulatory network in lower extremities arterial disease","volume":"10","author":"Zalewski","year":"2019","journal-title":"Front. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Morelli, V.M., Br\u00e6kkan, S.K., and Hansen, J.-B. (2020). Role of microRNAs in venous thromboembolism. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072602"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1053\/j.semvascsurg.2013.04.003","article-title":"Genomics of varicose veins and chronic venous insufficiency","volume":"26","author":"Markovic","year":"2013","journal-title":"Semin. Vasc. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1620\/tjem.228.341","article-title":"MicroRNA profiling in great saphenous vein tissues of patients with chronic venous insufficiency","volume":"228","author":"Cui","year":"2012","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29324","DOI":"10.1074\/jbc.M112.382135","article-title":"Induction of specific microRNAs inhibits cutaneous wound healing","volume":"287","author":"Pastar","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.avsg.2013.04.001","article-title":"Analysis of the association between an insertion\/deletion polymorphism within the 3\u2032 untranslated region of COL1A2 and chronic venous insufficiency","volume":"27","author":"Jin","year":"2013","journal-title":"Ann. Vasc. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1021\/ac960321m","article-title":"Elimination of uninformative variables for multivariate calibration","volume":"68","author":"Centner","year":"1996","journal-title":"Anal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.chemolab.2012.07.010","article-title":"A review of variable selection methods in Partial Least Squares Regression","volume":"118","author":"Mehmood","year":"2012","journal-title":"Chemometr. Intell. Lab. Syst."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chen, H., and Boutros, P.C. (2011). VennDiagram: A package for the generation of highly-customizable Venn and Euler diagrams in R. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-35"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v008.i11","article-title":"Scatterplot3d\u2014An R package for visualizing multivariate data","volume":"8","author":"Ligges","year":"2003","journal-title":"J. Stat. Softw."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.C., and M\u00fcller, M. (2011). pROC: An open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-77"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13073-019-0638-6","article-title":"Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data","volume":"11","author":"Finotello","year":"2019","journal-title":"Genome Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"i436","DOI":"10.1093\/bioinformatics\/btz363","article-title":"Comprehensive evaluation of transcriptome-based cell-type quantification methods for immuno-oncology","volume":"35","author":"Sturm","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1093\/nar\/gku631","article-title":"The multiMiR R package and database: Integration of microRNA\u2013target interactions along with their disease and drug associations","volume":"42","author":"Ru","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2S","DOI":"10.1016\/j.jvs.2011.01.079","article-title":"The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum","volume":"53","author":"Gloviczki","year":"2011","journal-title":"J. Vasc. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e138","DOI":"10.1038\/emm.2014.81","article-title":"MiR-34a, miR-21 and miR-23a as potential biomarkers for coronary artery disease: A pilot microarray study and confirmation in a 32 patient cohort","volume":"47","author":"Han","year":"2015","journal-title":"Exp. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.atherosclerosis.2011.07.020","article-title":"miR-21, miR-210, miR-34a, and miR-146a\/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study","volume":"219","author":"Raitoharju","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Walias, F.J., V\u00e1zquez, E., Pacheco, Y., Rodr\u00edguez-Fern\u00e1ndez, J.M., P\u00e9rez-El\u00edas, M.J., Dronda, F., Casado, J.L., Moreno, A., Hermida, J.M., and Quereda, C. (2020). Risk, diagnostic and predictor factors for classical hodgkin lymphoma in HIV-1-infected individuals: Role of plasma exosome-derived miR-20a and miR-21. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030760"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Irimie-Aghiorghiesei, A.I., Pop-Bica, C., Pintea, S., Braicu, C., Cojocneanu, R., Zim\u021ba, A.-A., Gulei, D., Slab\u00fd, O., and Berindan-Neagoe, I. (2019). Prognostic Value of MiR-21: An updated meta-analysis in Head and Neck Squamous Cell Carcinoma (HNSCC). J. Clin. Med., 8.","DOI":"10.3390\/jcm8122041"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Shi, J. (2016). Considering exosomal miR-21 as a biomarker for cancer. J. Clin. Med., 5.","DOI":"10.3390\/jcm5040042"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ulivi, P., Petracci, E., Marisi, G., Baglivo, S., Chiari, R., Billi, M., Canale, M., Pasini, L., Racanicchi, S., and Vagheggini, A. (2019). Prognostic role of circulating miRNAs in early-stage non-small cell lung cancer. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020131"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.3390\/jcm4111951","article-title":"microRNA-34a as a therapeutic agent against human cancer","volume":"4","author":"Saito","year":"2015","journal-title":"J. Clin. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1159\/000106189","article-title":"Identification of differentially expressed genes in human varicose veins: Involvement of matrix gla protein in extracellular matrix remodeling","volume":"44","author":"Boularan","year":"2007","journal-title":"J. Vasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jaad.2008.07.018","article-title":"A gene signature of nonhealing venous ulcers: Potential diagnostic markers","volume":"59","author":"Charles","year":"2008","journal-title":"J. Am. Acad Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S1877-8607(10)60005-7","article-title":"Apoptosis and angiogenesis in varicose veins using gene expression profiling","volume":"1","author":"Chang","year":"2009","journal-title":"Fooyin J. Health Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hsieh, C.S., Tsai, C.T., Chen, Y.H., Chang, S.N., Hwang, J.J., Chuang, E.Y., and Wu, I.H. (2018). Global expression profiling identifies a novel hyaluronan synthases 2 gene in the pathogenesis of lower extremity varicose veins. J. Clin. Med., 7.","DOI":"10.3390\/jcm7120537"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"15999","DOI":"10.1073\/pnas.1419057111","article-title":"Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK","volume":"111","author":"Dbouk","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tcm.2013.09.002","article-title":"Role of miR-181 family in regulating vascular inflammation and immunity","volume":"24","author":"Sun","year":"2014","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Xie, W., Li, M., Xu, N., Lv, Q., Huang, N., He, J., and Zhang, Y. (2013). MiR-181a regulates inflammation responses in monocytes and macrophages. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058639"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6996","DOI":"10.1002\/jcp.26622","article-title":"MiR-181a inhibits vascular inflammation induced by ox-LDL via targeting TLR4 in human macrophages","volume":"233","author":"Du","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1159\/000453209","article-title":"Circulating miR-181a as a potential novel biomarker for diagnosis of acute myocardial infarction","volume":"40","author":"Zhu","year":"2016","journal-title":"Cell Physiol. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jprot.2015.05.023","article-title":"Quantitative and integrated proteome and microRNA analysis of endothelial replicative senescence","volume":"126","author":"Yentrapalli","year":"2015","journal-title":"J. Proteomics."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/15569527.2017.1355314","article-title":"Evaluation of microRNA responses in ARPE-19 cells against the oxidative stress","volume":"37","author":"Ayaz","year":"2018","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.biocel.2018.05.006","article-title":"MiR-128-3p directly targets VEGFC\/VEGFR3 to modulate the proliferation of lymphatic endothelial cells through Ca(2+) signaling","volume":"102","author":"Zhou","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"BSR20180540","DOI":"10.1042\/BSR20180540","article-title":"Decreased MiR-128-3p alleviates the progression of rheumatoid arthritis by up-regulating the expression of TNFAIP3","volume":"38","author":"Xia","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1007\/s12010-015-1680-5","article-title":"Identification of lncRNA MEG3 binding protein using MS2-Tagged RNA affinity purification and mass spectrometry","volume":"176","author":"Liu","year":"2015","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5119","DOI":"10.1210\/jc.2003-030222","article-title":"A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells","volume":"88","author":"Zhang","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"24731","DOI":"10.1074\/jbc.M702029200","article-title":"Activation of p53 by MEG3 non-coding RNA","volume":"282","author":"Zhou","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1002\/jcb.26304","article-title":"Knockdown of long non-coding RNA MEG3 protects H9c2 cells from hypoxia-induced injury by targeting microRNA-183","volume":"119","author":"Gong","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/aps.2017.56","article-title":"WNK1 is required for proliferation induced by hypotonic challenge in rat vascular smooth muscle cells","volume":"39","author":"Zhang","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9013","DOI":"10.2147\/OTT.S183847","article-title":"MicroRNA-769 is downregulated in colorectal cancer and inhibits cancer progression by directly targeting cyclin-dependent kinase 1","volume":"11","author":"Wang","year":"2018","journal-title":"Onco Targets Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"113558","DOI":"10.18632\/oncotarget.23060","article-title":"MiR-769-5p suppressed cell proliferation, migration and invasion by targeting TGFBR1 in non-small cell lung carcinoma","volume":"8","author":"Yang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Busch, A., Busch, M., Scholz, C.J., Kellersmann, R., Otto, C., Chernogubova, E., Maegdefessel, L., Zernecke, A., and Lorenz, U. (2016). Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010081"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1161\/ATVBAHA.107.151704","article-title":"Angiotensin II stimulates protein kinase D-dependent histone deacetylase 5 phosphorylation and nuclear export leading to vascular smooth muscle cell hypertrophy","volume":"27","author":"Xu","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.12659\/MSM.898883","article-title":"MiR-206 suppresses the progression of coronary artery disease by modulating Vascular Endothelial Growth Factor (VEGF) Expression","volume":"22","author":"Wang","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1242\/dev.083774","article-title":"MiR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish","volume":"139","author":"Stahlhut","year":"2012","journal-title":"Development"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lai, J.G., Tsai, S.M., Tu, H.C., Chen, W.C., Kou, F.J., Lu, J.W., Wang, H.D., Huang, C.L., and Yuh, C.H. (2014). Zebrafish WNK lysine deficient protein kinase 1 (wnk1) affects angiogenesis associated with VEGF signaling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106129"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1182\/blood-2012-02-408328","article-title":"CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis","volume":"120","author":"Pan","year":"2012","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S1535-6108(03)00187-9","article-title":"TSC2 regulates VEGF through mTOR-dependent and -independent pathways","volume":"4","author":"Brugarolas","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/sj.onc.1205108","article-title":"Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling","volume":"21","author":"Deroanne","year":"2002","journal-title":"Oncogene"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.1182\/blood-2009-01-196485","article-title":"HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells","volume":"113","author":"Urbich","year":"2009","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1159\/000485905","article-title":"Potential involvement of mir-30e-3p in myocardial injury induced by coronary microembolization via autophagy activation","volume":"44","author":"Wang","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11033-016-4082-z","article-title":"Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group","volume":"44","author":"Kim","year":"2017","journal-title":"Mol. Biol. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"430","DOI":"10.5551\/jat.35923","article-title":"Potential role of lipometabolism-related micrornas in peripheral blood mononuclear cells as biomarkers for coronary artery disease","volume":"24","author":"Dong","year":"2017","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.diabres.2018.03.024","article-title":"B-RCA revealed circulating miR-33a\/b associates with serum cholesterol in type 2 diabetes patients at high risk of ASCVD","volume":"140","author":"Deng","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13195-019-0501-4","article-title":"Altered microRNAs related to synaptic function as potential plasma biomarkers for Alzheimer\u2019s disease","volume":"11","author":"Clarimon","year":"2019","journal-title":"Alzheimers Res. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.psychres.2018.03.080","article-title":"Identification of miR-22-3p, miR-92a-3p, and miR-137 in peripheral blood as biomarker for schizophrenia","volume":"265","author":"Ma","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.neulet.2013.10.041","article-title":"Expression of proline-rich coiled-coil 2B protein in developing rat brains","volume":"557 Pt B","author":"Mei","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Fujii, T., Shimada, K., Nakai, T., and Ohbayashi, C. (2018). MicroRNAs in smoking-related carcinogenesis: Biomarkers, functions, and therapy. J. Clin. Med., 7.","DOI":"10.3390\/jcm7050098"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/5\/1251\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:51:18Z","timestamp":1760363478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/5\/1251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,25]]},"references-count":93,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["jcm9051251"],"URL":"https:\/\/doi.org\/10.3390\/jcm9051251","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,25]]}}}