Circulating Long Noncoding RNA, LIPCAR, Predicts Survival in Patients With Heart Failure

Abstract

Objective: To study the role of long noncoding RNAs as potential biomarkers in heart disease. Methods and Results: Global transcriptomic analyses were done in plasma RNA from patients with or without left ventricular remodeling after myocardial infarction. Regulated candidates were validated in 3 independent patient cohorts developing cardiac remodeling and heart failure (788 patients). The mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) was downregulated early after myocardial infarction but upregulated during later stages. LIPCAR levels identified patients developing cardiac remodeling and were independently to other risk markers associated with future cardiovascular deaths. Key Words: cardiac biomarkers ■ cardiac remodeling ■ circulating lncRNA ■ heart failure ■ mitochondria ■ myocardial infarction ■ RNA, long noncoding Conclusions: LIPCAR isOriginal received March 10, 2014; revision received March 20, 2014; accepted March 24, 2014. In February 2014, the average time from submission to first decision for all original research papers submitted to Circulation Research was 13.8 days.Brief UltraRapid Communications are designed to be a format for manuscripts that are of outstanding interest to the readership, report definitive observations, but have a relatively narrow scope. Less comprehensive than Regular Articles but still scientifically rigorous, BURCs present seminal findings that have the potential to open up new avenues of research. A decision on BURCs is rendered within 7 days of submission.From the Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx (R.K., I.V., J.F., A.H., T.T.) and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Hannover, Germany; Inserm, U744, University Lille Nord de France, Lille, France (C.B., F.M., G.L., P.d.G., F.P.); Institut Pasteur de Lille, Lille, France (C.B., F.M., G.L., P.d.G., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (C.B., G.L., P.d.G., F.P.); Faculté de Médecine de Lille, Lille, France (C.B., G.L.); and National Heart and Lung Institute, Imperial College London, London, United Kingdom (T.T. Methods Populations of Patients With HFThe strategy of lncRNA screening and validation is depicted in Figure 1A. A potential association between detectable lncRNAs in EDTA-plasma and presence of future LV remodeling post MI was analyzed in the REmodelage VEntriculaire (REVE)-2 cohort. This prospective multicenter study was designed to analyze the association between circulating biomarkers and LV remodeling. 15 A total of 246 patients with a first anterior wall Q-wave MI have been enrolled from February 2006 to September 2008. Inclusion criteria were hospitalization within 24 hours after symptom onset and ≥3 akinetic LV segments in the infarct zone at the predischarge echocardiography. Exclusion criteria were inadequate echocardiographic image quality, life-limiting noncardiac disease, significant valvular disease, or prior Q-wave MI. The protocol required serial echographic studies at hospital discharge ...

Long non-coding RNAs link extracellular matrix gene expression to ischemic cardiomyopathy

“…Interestingly, another recent study identified a novel circulating lncRNA, LIPCAR, as a molecular marker for HF. 32 Our study, together with these prior reports, indicates that lncRNAs are a novel class of regulators and biomarkers for cardiovascular biology and diseases.…”

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

“…This review also describes the finding of mitochondrial lncRNAs in different cell types such as HeLa cells, breast cells and ventricular tissue [34,35,36], fulfilling different roles as regulators of translation or as novel biomarkers of disease progression. Among these, LIPCAR (Long Intergenic noncoding RNA Predicting CARdiac remodeling) is worthy of mention, as it is upregulated at late stages of left ventricular remodeling and is elevated in patients with chronic heart failure, suggesting this mtlncRNA as a prognostic indicator for cardiovascular mortality [37].…”

Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers

“…S1) were shown to contribute to muscle or myocardial function (8, 9). miRNAs and other classes of RNA have been profiled in failing human myocardium (10)(11)(12)(13)(14)(15)(16)(17), and a selected subset was also investigated as circulating biomarkers in HF (18)(19)(20)(21)(22)(23)(24). However, in these studies heart tissue and circulating miRNA abundance changes were not acquired simultaneously to correlate changes in tissue versus circulating miRNA composition.…”