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Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes
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 coronar...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094571/ https://www.ncbi.nlm.nih.gov/pubmed/30111293 http://dx.doi.org/10.1186/s12872-018-0894-1 |
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author | Marks, Edward C. A. Wilkinson, Tom M. Frampton, Chris M. Skelton, Lorraine Pilbrow, Anna P. Yandle, Tim G. Pemberton, Chris J. Doughty, Robert N. Whalley, Gillian A. Ellis, Chris J. Troughton, Richard W. Owen, Maurice C. Pattinson, Neil R. Cameron, Vicky A. Richards, A. Mark Gieseg, Steven P. Palmer, Barry R. |
author_facet | Marks, Edward C. A. Wilkinson, Tom M. Frampton, Chris M. Skelton, Lorraine Pilbrow, Anna P. Yandle, Tim G. Pemberton, Chris J. Doughty, Robert N. Whalley, Gillian A. Ellis, Chris J. Troughton, Richard W. Owen, Maurice C. Pattinson, Neil R. Cameron, Vicky A. Richards, A. Mark Gieseg, Steven P. Palmer, Barry R. |
author_sort | Marks, Edward C. A. |
collection | PubMed |
description | 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. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628. 16 September 2005, Retrospectively registered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12872-018-0894-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6094571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60945712018-08-24 Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes Marks, Edward C. A. Wilkinson, Tom M. Frampton, Chris M. Skelton, Lorraine Pilbrow, Anna P. Yandle, Tim G. Pemberton, Chris J. Doughty, Robert N. Whalley, Gillian A. Ellis, Chris J. Troughton, Richard W. Owen, Maurice C. Pattinson, Neil R. Cameron, Vicky A. Richards, A. Mark Gieseg, Steven P. Palmer, Barry R. BMC Cardiovasc Disord Research Article 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. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628. 16 September 2005, Retrospectively registered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12872-018-0894-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-15 /pmc/articles/PMC6094571/ /pubmed/30111293 http://dx.doi.org/10.1186/s12872-018-0894-1 Text en © The Author(s). 2018 Open AccessThis 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. |
spellingShingle | Research Article Marks, Edward C. A. Wilkinson, Tom M. Frampton, Chris M. Skelton, Lorraine Pilbrow, Anna P. Yandle, Tim G. Pemberton, Chris J. Doughty, Robert N. Whalley, Gillian A. Ellis, Chris J. Troughton, Richard W. Owen, Maurice C. Pattinson, Neil R. Cameron, Vicky A. Richards, A. Mark Gieseg, Steven P. Palmer, Barry R. Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes |
title | Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes |
title_full | Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes |
title_fullStr | Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes |
title_full_unstemmed | Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes |
title_short | Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes |
title_sort | plasma levels of soluble vegf receptor isoforms, circulating pterins and vegf system snps as prognostic biomarkers in patients with acute coronary syndromes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094571/ https://www.ncbi.nlm.nih.gov/pubmed/30111293 http://dx.doi.org/10.1186/s12872-018-0894-1 |
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