Long Noncoding RNAs in Patients With Acute Myocardial Infarction

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.

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

“…For the first time, we provided the clinical evidence that ANRIL level is associated with IL6/IL8 levels in blood, which further confirmed the pathological role of ANRIL relevant to CAD etiology. 50 Among the patients with detectable TNF-a, the significant correlation between TNF-a in serum and ANRIL/IL6/IL8 in PBMCs was not observed, in contrary to the grouping approach we described in Fig. 5A.…”

Non-coding RNAs in muscle differentiation and musculoskeletal disease

“…To date, alteration of lncRNA levels in plasma has been reported only in heart failure in humans and mice (66)(67)(68).…”

Potentiel des ARN non codants comme biomarqueurs dans l’insuffisance cardiaque

“…Il ne faut cependant pas oublier que pour déterminer un profil à haut risque de mortalité précoce chez les patients insuffisants cardiaques, plusieurs cibles géno-miques, protéomiques, métabolomiques et environnementales seront sûrement nécessaires. Très récemment, en utilisant une approche protéomique sans a priori sur les groupes cas-témoin de la cohorte INCA ainsi que différentes méthodes de régression statistique, nous avons établi un score de risque qui prédit la mortalité précoce chez les patients insuffisants cardiaques [32] [28]. Toutefois, certains des lncARN testés ont été impliqués dans d'autres pathologies, telles que le cancer, et ne sont donc pas spécifiques des pathologies cardiaques.…”