{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:18:39Z","timestamp":1787897919756,"version":"build-2784847793"},"reference-count":31,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["M2578-B30"],"award-info":[{"award-number":["M2578-B30"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In addition to supervised walking therapy, antithrombotic therapy and the management of risk factors, the treatment of peripheral artery disease (PAD) is limited to endovascular and surgical interventions, i.e., angioplasty with stent implantation and bypass surgery, respectively. Both are associated with a high restenosis rate. Furthermore, patients with PAD often suffer atherothrombotic events like myocardial infarction, transient ischemic attacks or stroke. Small ribonucleic acids (RNAs) have proven reliable biomarkers because of their remarkable stability. Small nucleolar RNAs (snoRNAs) guide modifications to small nuclear RNAs and ribosomal RNAs, enabling protein synthesis. In the current study, we measured four snoRNAs in 104 consecutive PAD patients who underwent elective infrainguinal angioplasty with stent implantation. We selected snoRNAs that showed significant overexpression in the plasma of end-stage PAD patients in a previous study. All four snoRNAs are transcribed from the 14q32 locus, which is strongly linked to human cardiovascular disease, including PAD and restenosis. We showed that the four selected 14q32 snoRNAs were abundantly expressed in the plasma of PAD patients. The plasma levels of these snoRNAs were not directly associated with target vessel restenosis, however, levels of SNORD113.2 and SNORD114.1 were strongly linked to platelet activation, which is an important determinant of long-term outcome, in PAD, and in cardiovascular disease in general.<\/jats:p>","DOI":"10.3390\/ijms20235975","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T11:07:00Z","timestamp":1574852820000},"page":"5975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Plasma Levels of snoRNAs are Associated with Platelet Activation in Patients with Peripheral Artery Disease"],"prefix":"10.3390","volume":"20","author":[{"given":"Anne Ya\u00ebl","family":"Nossent","sequence":"first","affiliation":[{"name":"Department for Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Ektefaie","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Wojta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Core Facilities, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Ludwig Boltzmann Cluster for Cardiovascular Research, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Eichelberger","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Panzer","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9554-7292","authenticated-orcid":false,"given":"Thomas","family":"Gremmel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Internal Medicine, Cardiology and Nephrology, Landesklinikum Wiener Neustadt, 2700 Wiener Neustadt, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1161\/CIRCULATIONAHA.108.191171","article-title":"Atherosclerotic Peripheral Vascular Disease Symposium II: Nomenclature for vascular diseases","volume":"118","author":"Hiatt","year":"2008","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1161\/CIRCRESAHA.116.303566","article-title":"Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease","volume":"116","author":"Hiatt","year":"2015","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nrcardio.2011.132","article-title":"Restenosis after PCI. Part 1: Pathophysiology and risk factors","volume":"9","author":"Jukema","year":"2011","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1161\/01.CIR.0000143102.38256.DE","article-title":"Improved prediction of fatal myocardial infarction using the ankle brachial index in addition to conventional risk factors: The Edinburgh Artery Study","volume":"110","author":"Lee","year":"2004","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1093\/eurheartj\/ehl092","article-title":"Association of low ankle brachial index with high mortality in primary care","volume":"27","author":"Diehm","year":"2006","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.atherosclerosis.2018.01.020","article-title":"Circulating microRNAs identify patients at increased risk of in-stent restenosis after peripheral angioplasty with stent implantation","volume":"269","author":"Stojkovic","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1161\/CIRCGENETICS.111.000053","article-title":"Differential microRNA expression profiles in peripheral arterial disease","volume":"6","author":"Stather","year":"2013","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10513","DOI":"10.1073\/pnas.0804549105","article-title":"Circulating microRNAs as stable blood-based markers for cancer detection","volume":"105","author":"Mitchell","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.3389\/fphys.2018.01136","article-title":"Circulating Small Non-coding RNAs as Biomarkers for Recovery After Exhaustive or Repetitive Exercise","volume":"9","author":"Hakansson","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hakansson, K.E.J., Goossens, E.A.C., Trompet, S., van Ingen, E., de Vries, M.R., van der Kwast, R., Ripa, R.S., Kastrup, J., Hohensinner, P.J., and Kaun, C. (2018). Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvy309"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1093\/emboj\/20.14.3617","article-title":"Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs","volume":"20","author":"Kiss","year":"2001","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1097\/SLA.0000000000001466","article-title":"Inhibition of MicroRNA-494 Reduces Carotid Artery Atherosclerotic Lesion Development and Increases Plaque Stability","volume":"262","author":"Wezel","year":"2015","journal-title":"Ann. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1161\/CIRCRESAHA.114.304747","article-title":"Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494 and miR-495 increases neovascularization and blood flow recovery after ischemia","volume":"115","author":"Welten","year":"2014","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/cvr\/cvw039","article-title":"The multifactorial nature of microRNAs in vascular remodelling","volume":"110","author":"Welten","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.atherosclerosis.2017.04.011","article-title":"Inhibition of 14q32 microRNA miR-495 reduces lesion formation, intimal hyperplasia and plasma cholesterol levels in experimental restenosis","volume":"261","author":"Welten","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1097\/SLA.0b013e3182a6aac0","article-title":"The 14q32 microRNA-487b targets the antiapoptotic insulin receptor substrate 1 in hypertension-induced remodeling of the aorta","volume":"258","author":"Nossent","year":"2013","journal-title":"Ann. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.jacc.2007.11.077","article-title":"Long-term prognosis of patients with peripheral arterial disease: A comparison in patients with coronary artery disease","volume":"51","author":"Welten","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.atherosclerosis.2013.10.027","article-title":"Response to antiplatelet therapy and platelet reactivity to thrombin receptor activating peptide-6 in cardiovascular interventions: Differences between peripheral and coronary angioplasty","volume":"232","author":"Gremmel","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1172\/JCI61271","article-title":"Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis","volume":"123","author":"Xi","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.thromres.2009.06.012","article-title":"Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy","volume":"124","author":"Gremmel","year":"2009","journal-title":"Thromb. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jacc.2008.04.045","article-title":"The association of cigarette smoking with enhanced platelet inhibition by clopidogrel","volume":"52","author":"Bliden","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1161\/ATVBAHA.113.302919","article-title":"Platelets mediate oxidized low-density lipoprotein-induced monocyte extravasation and foam cell formation","volume":"34","author":"Badrnya","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.omtn.2019.09.021","article-title":"Antisense Oligonucleotide Inhibition of MicroRNA-494 Halts Atherosclerotic Plaque Progression and Promotes Plaque Stabilization","volume":"18","author":"Foks","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/nm.3385","article-title":"Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c","volume":"19","author":"Edelstein","year":"2013","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1093\/nar\/gkw386","article-title":"An updated human snoRNAome","volume":"44","author":"Jorjani","year":"2016","journal-title":"Nucleic. Acids. Res."},{"key":"ref_26","first-page":"474","article-title":"In vivo and protease-activated receptor-1-mediated platelet activation but not response to antiplatelet therapy predict two-year outcomes after peripheral angioplasty with stent implantation","volume":"111","author":"Gremmel","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1160\/TH08-09-0577","article-title":"Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation","volume":"101","author":"Gremmel","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gremmel, T., Koppensteiner, R., and Panzer, S. (2015). Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists\u2014Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129666"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1160\/th15-07-0598","article-title":"Platelet-specific markers are associated with monocyte-platelet aggregate formation and thrombin generation potential in advanced atherosclerosis","volume":"115","author":"Gremmel","year":"2016","journal-title":"Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1160\/TH11-03-0137","article-title":"Clinical, genetic and confounding factors determine the dynamics of the in vitro response\/non response to clopidogrel","volume":"106","author":"Gremmel","year":"2011","journal-title":"Thromb. Haemost."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1093\/hmg\/11.13.1527","article-title":"Identification of tandemly-repeated C\/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi\/Angelman syndrome region","volume":"11","author":"Cavaille","year":"2002","journal-title":"Hum. Mol. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/23\/5975\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:37:54Z","timestamp":1760189874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/23\/5975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,27]]},"references-count":31,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["ijms20235975"],"URL":"https:\/\/doi.org\/10.3390\/ijms20235975","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,27]]}}}