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 ...
Reactive oxygen species (ROS) are subcellular messengers in signal transductions pathways with both beneficial and deleterious roles. ROS are generated as a by-product of mitochondrial respiration or metabolism or by specific enzymes such as superoxide dismutases, glutathione peroxidase, catalase, peroxiredoxins, and myeloperoxidases. Under physiological conditions, the low levels of ROS production are equivalent to their detoxification, playing a major role in cellular signaling and function. In pathological situations, particularly atherosclerosis or hypertension, the release of ROS exceeds endogenous antioxidant capacity, leading to cell death. At cardiovascular levels, oxidative stress is highly implicated in myocardial infarction, ischemia/reperfusion, or heart failure. Here, we will first detail the physiological role of low ROS production in the heart and the vessels. Indeed, ROS are able to regulate multiple cardiovascular functions, such as cell proliferation, migration, and death. Second, we will investigate the implication of oxidative stress in cardiovascular diseases. Then, we will focus on ROS produced by NAPDH oxidase or during endothelial or mitochondrial dysfunction. Given the importance of oxidative stress at the cardiovascular level, antioxidant therapies could be a real benefit. In the last part of this review, we will detail the new therapeutic strategies potentially involved in cardiovascular protection and currently under study.
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