TY - JOUR
T1 - Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction
AU - Devaux, Yvan
AU - Bousquenaud, Melanie
AU - Rodius, Sophie
AU - Marie, Pierre Yves
AU - Maskali, Fatiha
AU - Zhang, Lu
AU - Azuaje, Francisco
AU - Wagner, Daniel R.
N1 - Funding Information:
We thank Céline Jeanty, Malou Gloesener and Loredana Jacobs for expert technical assistance. This study was supported by grants from the Society for Research on Cardiovascular Diseases, the Ministry of Culture, Higher Education and Research, and the National Funds of Research of Luxembourg. M.B. is recipient of a fellowship from the National Funds of Research of Luxembourg (grant # PhD-AFR 08-024).
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=82655180611&partnerID=8YFLogxK
U2 - 10.1186/1755-8794-4-83
DO - 10.1186/1755-8794-4-83
M3 - Article
C2 - 22136666
AN - SCOPUS:82655180611
SN - 1755-8794
VL - 4
JO - BMC Medical Genomics
JF - BMC Medical Genomics
M1 - 83
ER -