Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes

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dc.contributor.authorMarks ECA
dc.contributor.authorWilkinson TM
dc.contributor.authorFrampton CM
dc.contributor.authorSkelton L
dc.contributor.authorPilbrow AP
dc.contributor.authorYandle TG
dc.contributor.authorPemberton CJ
dc.contributor.authorDoughty RN
dc.contributor.authorWhalley GA
dc.contributor.authorEllis CJ
dc.contributor.authorTroughton RW
dc.contributor.authorOwen MC
dc.contributor.authorPattinson NR
dc.contributor.authorCameron VA
dc.contributor.authorRichards AM
dc.contributor.authorGieseg SP
dc.contributor.authorPalmer BR
dc.date.accessioned2018-12-17T22:28:33Z
dc.date.available2018-12-17T22:28:33Z
dc.date.issued2018en
dc.date.updated2018-10-31T19:42:17Z
dc.description.abstract© 2018 The Author(s). Background: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. Methods: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042). Results: At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027). Conclusions: sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients.en
dc.identifier.doihttps://doi.org/10.1186/s12872-018-0894-1
dc.identifier.issn1471-2261
dc.identifier.issn1471-2261
dc.identifier.urihttp://hdl.handle.net/10092/16372
dc.languageEnglish
dc.language.isoen
dc.rights© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectsFlt-1en
dc.subjectKDRen
dc.subjectNeopterinen
dc.subjectAcute coronary syndromesen
dc.subjectMortalityen
dc.subjectPrognosisen
dc.subject.anzsrcFields of Research::32 - Biomedical and clinical sciences::3201 - Cardiovascular medicine and haematology::320101 - Cardiology (incl. cardiovascular diseases)en
dc.titlePlasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromesen
dc.typeJournal Articleen
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