TY - JOUR
T1 - Long noncoding RNAs in patients with acute myocardial infarction
AU - Vausort, Mélanie
AU - Wagner, Daniel R.
AU - Devaux, Yvan
N1 - Publisher Copyright:
© 2014 American Heart Association, Inc.
PY - 2014/9/12
Y1 - 2014/9/12
N2 - 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 metastasisassociated 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-STsegment. 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.
AB - 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 metastasisassociated 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-STsegment. 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.
KW - Long noncoding
KW - Myocardial infarction
KW - Prognosis
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=84910147922&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.115.303836
DO - 10.1161/CIRCRESAHA.115.303836
M3 - Article
C2 - 25035150
AN - SCOPUS:84910147922
SN - 0009-7330
VL - 115
SP - 668
EP - 677
JO - Circulation Research
JF - Circulation Research
IS - 7
ER -