{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:27:49Z","timestamp":1772490469157,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012623","name":"Federation of European Biochemical Societies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012623","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004564","name":"Ministarstvo Prosvete, Nauke i Tehnolo\u0161kog Razvoja","doi-asserted-by":"publisher","award":["175052"],"award-info":[{"award-number":["175052"]}],"id":[{"id":"10.13039\/501100004564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Deletion polymorphism of glutathione S\u2010transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end\u2010stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether <jats:italic>GSTM1-null<\/jats:italic> genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol\u2010binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C\u2010reactive protein (CRP), angiogenin, dickkopf\u20101 (Dkk\u20101), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein\u20101 (MCP\u20101), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM\u20101 and VCAM\u20101). In accordance with these findings, the levels of serum ICAM\u20101 and VCAM\u20101 (sICAM\u20101 and sVCAM\u20101) were increased in ESRD patients lacking GSTM1, in comparison with patients with the <jats:italic>GSTM1-active<\/jats:italic> genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD.<\/jats:p>","DOI":"10.1155\/2021\/6678924","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:20:39Z","timestamp":1611793239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1664-6557","authenticated-orcid":false,"given":"Djurdja","family":"Jerotic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Suvakov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Matic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelrahim","family":"Alqudah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Grieve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Pljesa-Ercegovac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Savic-Radojevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatjana","family":"Damjanovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nada","family":"Dimkovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-1014","authenticated-orcid":false,"given":"Lana","family":"McClements","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-5129","authenticated-orcid":false,"given":"Tatjana","family":"Simic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197403282901301"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030975"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/14.8.1934"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005121345"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005080834"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/15.2.218"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000189159.96900.d9"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs369"},{"key":"e_1_2_11_9_2","first-page":"1239","article-title":"Metabolic gene polymorphism frequencies in control populations","volume":"10","author":"Garte S.","year":"2001","journal-title":"Cancer Epidemiology and Prevention Biomarkers"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhh.2009.19"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/174182670200900104"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2007.02.014"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-007-0028-1"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-010-0330-5"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11070431"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-15-12"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000501300"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1999"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00568.2012"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017030228"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.139428"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)45228-9"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1515\/cclm.1974.12.10.444"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(98)00094-5"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1994.1233"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-017-1734-4"},{"key":"e_1_2_11_27_2","first-page":"233","article-title":"Alteration in plasma antioxidant capacity in various degrees of chronic renal failure","volume":"51","author":"Mimi\u0107-Oka J.","year":"1999","journal-title":"Clinical Nephrology"},{"key":"e_1_2_11_28_2","first-page":"44","article-title":"Erythrocyte glutathione peroxidase and superoxide dismutase activities in different stages of chronic renal failure","volume":"44","author":"Mimic-Oka J.","year":"1995","journal-title":"Clinical Nephrology"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.156"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-012-9595-4"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3038"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2008.00442.x"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.1159\/000502526"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.49.6.508"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm488"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.1159\/000299798"},{"key":"e_1_2_11_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2010.09.011"},{"key":"e_1_2_11_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9385"},{"key":"e_1_2_11_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90992-X"},{"key":"e_1_2_11_40_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-831051"},{"key":"e_1_2_11_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.1994.tb01382.x"},{"key":"e_1_2_11_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00820-12"},{"key":"e_1_2_11_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2010.07.063"},{"key":"e_1_2_11_44_2","first-page":"936","article-title":"Association between retinol-binding protein and renal function among Asian subjects with type 2 diabetes mellitus: a cross-sectional study","volume":"42","author":"Thawnashom K.","year":"2011","journal-title":"Southeast Asian Journal of Tropical Medicineand Public Health"},{"key":"e_1_2_11_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-7-29"},{"key":"e_1_2_11_46_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005050572"},{"key":"e_1_2_11_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.174821"},{"key":"e_1_2_11_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.11.e83"},{"key":"e_1_2_11_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.11.014"},{"key":"e_1_2_11_50_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013121283"},{"key":"e_1_2_11_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.166686"},{"key":"e_1_2_11_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.03.007"},{"key":"e_1_2_11_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007566"},{"key":"e_1_2_11_54_2","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2019050449"},{"key":"e_1_2_11_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.12.2043"},{"key":"e_1_2_11_56_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005561200"},{"key":"e_1_2_11_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.10.122"},{"key":"e_1_2_11_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00712-5"},{"key":"e_1_2_11_59_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/161346"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/6678924.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/6678924.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/6678924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T18:49:57Z","timestamp":1723056597000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/6678924"}},"subtitle":[],"editor":[{"given":"Gordana","family":"Kocic","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/6678924"],"URL":"https:\/\/doi.org\/10.1155\/2021\/6678924","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2020-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6678924"}}