Mélanie Vausort1, Daniel R Wagner1, Yvan Devaux2. 1. From the Laboratory of Cardiovascular Research, Centre de Recherche Public de la Santé, Luxembourg, Luxembourg (M.V., Y.D.); and Division of Cardiology, Centre Hospitalier, Luxembourg, Luxembourg (D.R.W.). 2. From the Laboratory of Cardiovascular Research, Centre de Recherche Public de la Santé, Luxembourg, Luxembourg (M.V., Y.D.); and Division of Cardiology, Centre Hospitalier, Luxembourg, Luxembourg (D.R.W.). yvan.devaux@crp-sante.lu.
Abstract
RATIONALE: Long noncoding RNAs (lncRNAs) constitute a novel class of noncoding RNAs that regulate gene expression. Although recent data suggest that lncRNAs may be associated with cardiac disease, little is known about lncRNAs in the setting of myocardial ischemia. OBJECTIVE: To measure lncRNAs in patients with myocardial infarction (MI). METHODS AND RESULTS: We enrolled 414 patients with acute MI treated by primary percutaneous coronary intervention. Blood samples were harvested at the time of reperfusion. Expression levels of 5 lncRNAs were measured in peripheral blood cells by quantitative polymerase chain reaction: hypoxia inducible factor 1A antisense RNA 2, cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL), potassium voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1), myocardial infarction-associated transcript, and metastasis-associated lung adenocarcinoma transcript 1. Levels of hypoxia inducible factor 1A antisense RNA 2, KCNQ1OT1, and metastasis-associated lung adenocarcinoma transcript 1 were higher in patients with MI than in healthy volunteers (P<0.01), and levels of ANRIL were lower in patients with MI (P=0.003). Patients with ST-segment-elevation MI had lower levels of ANRIL (P<0.001), KCNQ1OT1 (P<0.001), myocardial infarction-associated transcript (P<0.001), and metastasis-associated lung adenocarcinoma transcript 1 (P=0.005) when compared with patients with non-ST-segment-elevation MI. Levels of ANRIL were associated with age, diabetes mellitus, and hypertension. Patients presenting within 3 hours of chest pain onset had elevated levels of hypoxia inducible factor 1A antisense RNA 2 when compared with patients presenting later on. ANRIL, KCNQ1OT1, myocardial infarction-associated transcript, and metastasis-associated lung adenocarcinoma transcript 1 were significant univariable predictors of left ventricular dysfunction as assessed by an ejection fraction ≤40% at 4-month follow-up. In multivariable and reclassification analyses, ANRIL and KCNQ1OT1 improved the prediction of left ventricular dysfunction by a model, including demographic features, clinical parameters, and cardiac biomarkers. CONCLUSIONS: Levels of lncRNAs in blood cells are regulated after MI and may help in prediction of outcome. This motivates further investigation of the role of lncRNAs after MI.
RATIONALE: Long noncoding RNAs (lncRNAs) constitute a novel class of noncoding RNAs that regulate gene expression. Although recent data suggest that lncRNAs may be associated with cardiac disease, little is known about lncRNAs in the setting of myocardial ischemia. OBJECTIVE: To measure lncRNAs in patients with myocardial infarction (MI). METHODS AND RESULTS: We enrolled 414 patients with acute MI treated by primary percutaneous coronary intervention. Blood samples were harvested at the time of reperfusion. Expression levels of 5 lncRNAs were measured in peripheral blood cells by quantitative polymerase chain reaction: hypoxia inducible factor 1A antisense RNA 2, cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL), potassium voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1), myocardial infarction-associated transcript, and metastasis-associated lung adenocarcinoma transcript 1. Levels of hypoxia inducible factor 1A antisense RNA 2, KCNQ1OT1, and metastasis-associated lung adenocarcinoma transcript 1 were higher in patients with MI than in healthy volunteers (P<0.01), and levels of ANRIL were lower in patients with MI (P=0.003). Patients with ST-segment-elevation MI had lower levels of ANRIL (P<0.001), KCNQ1OT1 (P<0.001), myocardial infarction-associated transcript (P<0.001), and metastasis-associated lung adenocarcinoma transcript 1 (P=0.005) when compared with patients with non-ST-segment-elevation MI. Levels of ANRIL were associated with age, diabetes mellitus, and hypertension. Patients presenting within 3 hours of chest pain onset had elevated levels of hypoxia inducible factor 1A antisense RNA 2 when compared with patients presenting later on. ANRIL, KCNQ1OT1, myocardial infarction-associated transcript, and metastasis-associated lung adenocarcinoma transcript 1 were significant univariable predictors of left ventricular dysfunction as assessed by an ejection fraction ≤40% at 4-month follow-up. In multivariable and reclassification analyses, ANRIL and KCNQ1OT1 improved the prediction of left ventricular dysfunction by a model, including demographic features, clinical parameters, and cardiac biomarkers. CONCLUSIONS: Levels of lncRNAs in blood cells are regulated after MI and may help in prediction of outcome. This motivates further investigation of the role of lncRNAs after MI.
Authors: Wolfgang Poller; Stefanie Dimmeler; Stephane Heymans; Tanja Zeller; Jan Haas; Mahir Karakas; David-Manuel Leistner; Philipp Jakob; Shinichi Nakagawa; Stefan Blankenberg; Stefan Engelhardt; Thomas Thum; Christian Weber; Benjamin Meder; Roger Hajjar; Ulf Landmesser Journal: Eur Heart J Date: 2018-08-01 Impact factor: 29.983