Cargando…
Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction
BACKGROUND: Prediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers. METHODS: Blood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutane...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240818/ https://www.ncbi.nlm.nih.gov/pubmed/22136666 http://dx.doi.org/10.1186/1755-8794-4-83 |
_version_ | 1782219478559358976 |
---|---|
author | Devaux, Yvan Bousquenaud, Melanie Rodius, Sophie Marie, Pierre-Yves Maskali, Fatiha Zhang, Lu Azuaje, Francisco Wagner, Daniel R |
author_facet | Devaux, Yvan Bousquenaud, Melanie Rodius, Sophie Marie, Pierre-Yves Maskali, Fatiha Zhang, Lu Azuaje, Francisco Wagner, Daniel R |
author_sort | Devaux, Yvan |
collection | PubMed |
description | BACKGROUND: Prediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers. METHODS: Blood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutaneous coronary intervention. Messenger RNA was extracted from whole blood cells. LV function was evaluated by echocardiography at 4-months. RESULTS: In a test cohort of 32 MI patients, integrated analysis of microarrays with a network of protein-protein interactions identified subgroups of genes which predicted LV dysfunction (ejection fraction ≤ 40%) with areas under the receiver operating characteristic curve (AUC) above 0.80. Candidate genes included transforming growth factor beta receptor 1 (TGFBR1). In a validation cohort of 115 MI patients, TGBFR1 was up-regulated in patients with LV dysfunction (P < 0.001) and was associated with LV function at 4-months (P = 0.003). TGFBR1 predicted LV function with an AUC of 0.72, while peak levels of troponin T (TnT) provided an AUC of 0.64. Adding TGFBR1 to the prediction of TnT resulted in a net reclassification index of 8.2%. When added to a mixed clinical model including age, gender and time to reperfusion, TGFBR1 reclassified 17.7% of misclassified patients. TGFB1, the ligand of TGFBR1, was also up-regulated in patients with LV dysfunction (P = 0.004), was associated with LV function (P = 0.006), and provided an AUC of 0.66. In the rat MI model induced by permanent coronary ligation, the TGFB1-TGFBR1 axis was activated in the heart and correlated with the extent of remodeling at 2 months. CONCLUSIONS: We identified TGFBR1 as a new candidate prognostic biomarker after acute MI. |
format | Online Article Text |
id | pubmed-3240818 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32408182011-12-17 Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction Devaux, Yvan Bousquenaud, Melanie Rodius, Sophie Marie, Pierre-Yves Maskali, Fatiha Zhang, Lu Azuaje, Francisco Wagner, Daniel R BMC Med Genomics Research Article BACKGROUND: Prediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers. METHODS: Blood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutaneous coronary intervention. Messenger RNA was extracted from whole blood cells. LV function was evaluated by echocardiography at 4-months. RESULTS: In a test cohort of 32 MI patients, integrated analysis of microarrays with a network of protein-protein interactions identified subgroups of genes which predicted LV dysfunction (ejection fraction ≤ 40%) with areas under the receiver operating characteristic curve (AUC) above 0.80. Candidate genes included transforming growth factor beta receptor 1 (TGFBR1). In a validation cohort of 115 MI patients, TGBFR1 was up-regulated in patients with LV dysfunction (P < 0.001) and was associated with LV function at 4-months (P = 0.003). TGFBR1 predicted LV function with an AUC of 0.72, while peak levels of troponin T (TnT) provided an AUC of 0.64. Adding TGFBR1 to the prediction of TnT resulted in a net reclassification index of 8.2%. When added to a mixed clinical model including age, gender and time to reperfusion, TGFBR1 reclassified 17.7% of misclassified patients. TGFB1, the ligand of TGFBR1, was also up-regulated in patients with LV dysfunction (P = 0.004), was associated with LV function (P = 0.006), and provided an AUC of 0.66. In the rat MI model induced by permanent coronary ligation, the TGFB1-TGFBR1 axis was activated in the heart and correlated with the extent of remodeling at 2 months. CONCLUSIONS: We identified TGFBR1 as a new candidate prognostic biomarker after acute MI. BioMed Central 2011-12-05 /pmc/articles/PMC3240818/ /pubmed/22136666 http://dx.doi.org/10.1186/1755-8794-4-83 Text en Copyright ©2011 Devaux et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Devaux, Yvan Bousquenaud, Melanie Rodius, Sophie Marie, Pierre-Yves Maskali, Fatiha Zhang, Lu Azuaje, Francisco Wagner, Daniel R Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction |
title | Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction |
title_full | Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction |
title_fullStr | Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction |
title_full_unstemmed | Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction |
title_short | Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction |
title_sort | transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240818/ https://www.ncbi.nlm.nih.gov/pubmed/22136666 http://dx.doi.org/10.1186/1755-8794-4-83 |
work_keys_str_mv | AT devauxyvan transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction AT bousquenaudmelanie transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction AT rodiussophie transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction AT mariepierreyves transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction AT maskalifatiha transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction AT zhanglu transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction AT azuajefrancisco transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction AT wagnerdanielr transforminggrowthfactorbreceptor1isanewcandidateprognosticbiomarkerafteracutemyocardialinfarction |