{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:29:39Z","timestamp":1790879379764,"version":"4.1.0"},"reference-count":23,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microparticles (MPs) are small membrane vesicles released by stimulated or apoptotic cells, including the endothelium. Hyperhomocysteinemia (HHcy) is a blood disorder characterized by an increase in the plasma concentrations of total homocysteine (Hcy). The plasma Hcy level is determined by environmental factors (dietary habits, i.e. the intake of folic acid, FA) and genetic factors (N 5,N 10-methylenetetrahydro-folate reductase, MTHFR, polymorphism 677C&gt;T). To evaluate whether moderate Hcy concentrations induce endothelial MP formation, the role of FA supplementation and the influence of MTHFR polymorphism were analysed. Human umbilical vein endothelial cells (HUVEC) were treated in vitro with 50 \u03bcM of Hcy and methionine (Met). The MP number and apoptotic phenotype were analyzed using flow cytometry. Increasing doses of FA (5, 15 and 50 \u03bcM) were used to reduce the HHcy effect. The MTHFR 677C&gt;T polymorphism was determined. HUVEC stimulated by Hcy produced significantly more MPs than HUVEC under the control conditions: 3,551 \u00b1 620 vs 2,270 \u00b1 657 kMP (p = 0.02). Supplementation with FA at concentrations of 5, 15 and 50 \u03bcM reduced the MP count in the cell culture supernatant to 345 \u00b1 332, 873 \u00b1 329, and 688 \u00b1 453 kMP, respectively (p = 0.03). MTHFR 677C&gt;T heterozygosity was associated with a significant increase in MP formation after stimulation with Hcy compared to the control conditions: 3,617 \u00b1 152 vs 1,518 \u00b1 343 kMP (p = 0.02). Furthermore, the MTHFR genotype altered MP formation after Met loading. On average, 24% of the entire MP population was apoptotic (annexin V-positive). Endothelial function impairment due to HHcy is related to MP shedding, which may involve platelets and other blood and vascular cells. MP shedding is a physiological response to moderate HHcy.<\/jats:p>","DOI":"10.2478\/s11658-010-0040-2","type":"journal-article","created":{"date-parts":[[2010,12,15]],"date-time":"2010-12-15T16:07:43Z","timestamp":1292429263000},"source":"Crossref","is-referenced-by-count":23,"title":["Endothelial microparticle formation in moderate concentrations of homocysteine and methionine in vitro"],"prefix":"10.2478","volume":"16","author":[{"given":"Ma\u0142gorzata","family":"Seku\u0142a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Janawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Stankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"St\u0119pie\u0144","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref101","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1161\/01.CIR.0000033972.90653.AF","article-title":"Plasminogen activator inhibitor - promotes formation of endothelial microparticles with procoagulant potential http dx org","volume":"11","author":"Brodsky","year":"2002","journal-title":"Circulation"},{"key":"ref191","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1152\/ajpheart.01172.2003","article-title":"Endotheliumderived microparticles impair endothelial function in vitro http dx org","volume":"20","author":"Brodsky","year":"2004","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref181","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1111\/j.1538-7836.2006.01911.x","article-title":"Circulating endothelial microparticles in acute ischemic stroke : a link to severity , lesion volume and outcome http dx org","volume":"19","author":"Simak","year":"2006","journal-title":"Thromb Haemost"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1161\/STROKEAHA.108.529503","article-title":"Heart outcomes prevention evaluation investigators homocysteine - lowering therapy and stroke risk severity and disability : additional findings from the HOPE trial http dx org","volume":"3","author":"Saposnik","year":"2009","journal-title":"Stroke"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/sj.bjp.0705446","article-title":"Pharmacokinetic study on the utilization of - methyltetrahydrofolate and folic acid in patients with coronary artery disease http dx org","volume":"6","author":"Willems","year":"2004","journal-title":"Brit J Pharmacol"},{"key":"ref01","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00726-006-0432-9","article-title":"Mechanism of homocysteine toxicity in humans http dx org","volume":"1","author":"Per\u0142a","year":"2007","journal-title":"Amino Acids"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/BF03195624","article-title":"Homocystine MTHFR gene polymorphisms , and cardiocerebrovascular risk http dx org","volume":"5","author":"Trabetti","year":"2008","journal-title":"Appl Genet"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1139\/Y07-112","article-title":"Homocysteine stimulates NADPH oxidase - mediated superoxide production leading to endothelial dysfunction in rats Can http dx org","volume":"8","author":"Edirimanne","year":"2007","journal-title":"Physiol Pharmacol"},{"key":"ref211","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1042\/CS19980382","article-title":"Endothelial dysfunction by acute hyperhomocysteinemia : restoration by folic acid http dx org","volume":"22","author":"Usui","year":"1999","journal-title":"Clin Sci"},{"key":"ref201","first-page":"53","article-title":"Paradoxical augmentation of bradykinin - induced vasodilatation by xanthine \/ xanthine oxidase - derived free radicals in isolated guinea pig heart","volume":"21","author":"Olszanecki","year":"2002","journal-title":"Physiol Pharmacol"},{"key":"ref151","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.thromres.2005.01.013","article-title":"Detached endothelial cells and microparticles as sources of tissue factor activity http dx org","volume":"16","author":"Kushak","year":"2005","journal-title":"Thromb Res"},{"key":"ref11","first-page":"197","article-title":"Homocysteine and progression of coronary artery disease","volume":"2","author":"Skibi\u0144ska","year":"2004","journal-title":"Kardiol Pol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1161\/01.CIR.100.11.1161","article-title":"Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst inemia in humans","volume":"7","author":"Kanani","year":"1999","journal-title":"Circulation"},{"key":"ref161","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1152\/ajpheart.00842.2004","article-title":"Shed membrane microparticles from circulating and vascular cells in regulating vascular function http dx org","volume":"17","author":"Mart\u00ednez","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1177\/1076029610378499.","article-title":"Hyperhomocysteinemia prevalence among patients with venous thromboembolism","volume":"4","author":"K\u00f6kt\u00fcrk","year":"2010","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref141","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/j.chroma.2003.11.030","article-title":"Analysis of plasma thiols by high - performance liquid chromatography with ultraviolet detection http dx org","volume":"15","author":"Bald","year":"2004","journal-title":"Chromatography"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0049-3848(03)00064-1","article-title":"Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis http dx org","volume":"10","author":"Jimenez","year":"2003","journal-title":"Thromb Res"},{"key":"ref111","first-page":"39","article-title":"CD microparticles in healthy offsprings of patients with coronary artery disease http dx org","volume":"12","author":"Bulut","year":"2009","journal-title":"Eur Clin Invest"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1161\/hc4601.098514","article-title":"Homocysteine impairs the nitric oxide synthase pathway : role of asymmetric dimethylarginine http dx org","volume":"9","author":"St\u00fchlinger","year":"2001","journal-title":"Circulation"},{"key":"ref221","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/sj.ejhg.5201389","article-title":"den van Homocysteine levels before and after methionine loading in Dutch families http dx org","volume":"23","author":"Heijer","year":"2005","journal-title":"Eur Hum Genet"},{"key":"ref171","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0008-6363(98)00338-1","article-title":"den Familial hyperhomocysteinaemia and endothelium - dependent vasodilatation and arterial distensibility of large arteries http dx org","volume":"18","author":"Lambert","year":"1999","journal-title":"Cardiovasc Res"},{"key":"ref131","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1111\/j.1538-7836.2009.03540.x","article-title":"Levels of circulating endothelial progenitor cells are related to uremic toxins and vascular injury in hemodialysis patients http dx org","volume":"14","author":"Jourde","year":"2009","journal-title":"Thromb Haemost"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1111\/j.1538-7836.2005.01780.x","article-title":"Elevation of circulating endothelial microparticles in patients with chronic renal failure http dx org","volume":"13","author":"Faure","year":"2006","journal-title":"Thromb Haemost"}],"container-title":["Cellular and Molecular Biology Letters"],"original-title":[],"link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.2478\/s11658-010-0040-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.2478\/s11658-010-0040-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.2478\/s11658-010-0040-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T05:16:08Z","timestamp":1614834968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.2478\/s11658-010-0040-2\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,1]]},"references-count":23,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.2478\/s11658-010-0040-2","relation":{},"ISSN":["1689-1392"],"issn-type":[{"value":"1689-1392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,1]]}}}