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Purpose Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding RNAs, which regulate gene expression. Their role in cardiac disease is poorly known. Here, we investigated the association between lncRNAs and left ventricular hypertrophy. Methods Wild-type and adenosine A2A receptor overexpressing mice (A2A-Tg) were subjected to transverse aortic constriction (TAC) and expression of lncRNAs in the heart was investigated using genome-wide microarrays and an analytical pipeline specifically developed for lncRNAs. Results Microarray analysis identified two lncRNAs up-regulated and three down-regulated in the hearts of A2A-Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs 2900055J20Rik and Gm14005 were decreased in A2A-Tg mice (3.5- and 1.8-fold, p < 0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005 were increased in TAC mice compared to sham-operated animals (1.8- and 1.4-fold, after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2- and 1.6-fold (p < 0.01). Conclusions First, we have shown that data on lncRNAs can be obtained from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and Gm14005 is regulated after TAC and can be modulated by cardioprotective molecules. These observations motivate further investigation of the therapeutic value of lncRNAs in the heart. [ABSTRACT FROM AUTHOR]

The rat myocardial infarction (MI) model is widely used to study left ventricular (LV) remodeling. In this study, acipimox-enhanced (18)F-Fluorodeoxyglucose (FDG) gated-positron emission tomography (PET) was assessed for characterizing and predicting early remodeling in the rat infarct model. Nineteen Wistar rats had surgical occlusion of the left anterior descending coronary artery and 7 were sham-operated. PET was scheduled 48 h and 2 weeks later for quantifying MI area and LV function. Segments with <50% of FDG uptake had histological evidence of MI (74 ± 9% decrease in parietal thickness, fibrosis development). At 48 h, MI area was large (>35% of LV) in 6 rats, moderate (15-35% of LV) in 8 rats, limited (<15% of LV) in 5 rats and absent in the 7 sham rats. LV remodeling, assessed through the 2 weeks increase in end-diastolic volume, increased between rats with limited, moderate and large MI (+72 ± 25, +109 ± 56, +190 ± 69 μl, respectively, P = 0.007). This 3-groups classification allowed predicting 44% of the 2 weeks increase in end-diastolic volume, and additional 34% were predicted by heart rate at 48 h. The acipimox-enhanced FDG gated-PET technique provides efficient characterization and prediction of early remodeling in the rat infarct model. [ABSTRACT FROM AUTHOR]

Intracoronary infusion of autologous bone marrow cells (CTX) has been shown to improve myocardial function in post infarct patients and in patients with chronic ischemic cardiomyopathy. Whether CTX affects exercise-induced changes in cardiac deformation and mitral regurgitation (MR) in patients with end stage heart failure has not been studied. In this small pilot study, eleven patients with chronic ischemic cardiomyopathy, ejection fraction (EF) <25%, no inducible ischemia and heart failure class NYHA III underwent CTX. Symptom-limited bicycle exercise echocardiography was performed pre- and 4 months post CTX and maximum systolic strain (msyℇ), peak systolic strain rate (psysr) and effective regurgitant orifice of MR (ERO) were determined. There were no complications related to the procedure. The overall clinical benefit of CTX was limited with a trend towards improvement (NYHA 3.0±0.1 pre and 2.7±0.2 post CTX, p=0.06). The EF did not improve after CTX. The wall motion score index (WMSI) did not change at rest but decreased significantly during exercise (1.48±0.16 vs. 1.44±0.17, p=0.01). In conclusion, CTX may improve cardiac deformation and MR during exercise in patients with severe chronic heart failure when viable areas are targeted. [ABSTRACT FROM AUTHOR]

Focuses on a study which examined the effect of adenosine and its three cardiac receptors on the expression of interleukin-6 and interleukin-1beta in isolated rat cardiomyocytes and trabecular muscles obtained from patients with cardiomyopathy. Background on proinflammatory cytokines; Materials and methods; Results and discussion.

Background: Left ventricular (LV) remodeling after acute myocardial infarction is associated with adverse prognosis. MicroRNAs (miRNAs) regulate the expression of several genes involved in LV remodeling. Our aim was to identify miRNAs associated with LV remodeling after acute myocardial infarction., Methods and Results: We studied 90 patients after first ST-segment-elevation acute myocardial infarction. A derivation cohort consisted of 60 patients characterized by echocardiography predischarge and at 6-month follow-up. Thirty patients characterized by magnetic resonance imaging predischarge and at 4-month follow-up were the validation cohort. Remodeling was defined as an increase in LV end-diastolic volume (ΔEDV>0) between discharge and follow-up. Circulating miRNAs were measured by microarrays and polymerase chain reaction. Using a systems-based approach, we identified several miRNAs potentially involved in LV remodeling. In the derivation cohort, one of these miRNAs, miR-150, was downregulated in patients with remodeling (ΔEDV>0) compared with patients without remodeling (ΔEDV≤0). In the validation cohort, patients with remodeling had 2-fold lower levels of miR-150 than those without (P=0.03). miR-150 outperformed N-terminal pro-brain natriuretic peptide to predict remodeling (area under the receiver-operating characteristic curve of 0.74 and 0.60, respectively). miR-150 reclassified 54% (95% confidence interval, 5-102; P=0.03) of patients misclassified by N-terminal pro-brain natriuretic peptide and 59% (95% confidence interval, 9-108; P=0.02) of patients misclassified by a multiparameter clinical model, including age, sex, and admission levels of troponin I, creatine kinase, and N-terminal pro-brain natriuretic peptide., Conclusions: Low circulating levels of miR-150 are associated with LV remodeling after first ST-segment-elevation acute myocardial infarction. miR-150 has potential as a novel biomarker in this setting.

There is evidence that survival remains possible for infarction greater than 50% of the left ventricle in human, as well as in the rat infarct model. To our knowledge, survival has not been documented for infarctions involving the anterior, inferior and lateral wall leaving intact only the septal wall. An adult rat underwent a ligation of the left anterior descending coronary artery. ECG-triggered (18)F-ffluorodeoxyglucose Positron Emission Tomography revealed that 72% of the left ventricle was necrotic and totally akinetic. Although the left ventricular ejection fraction was severely impaired (9%), this rat survived and was asymptomatic after 2 months. The exact reasons for this incredible survival are still unclear.

Background: The CC-chemokine receptor 5 (CCR5) is regulating inflammatory pathways and may thus be implicated in the development and progression of heart failure (HF). A 32 base pair deletion of the ccr5 gene, called CCR5delta32, prevents the expression of CCR5 at the cell surface. We analyzed the association between the CCR5delta32 deletion and the risk and severity of myocardial infarction (MI) in a cohort of patients from Luxembourg., Methods: Using TaqMan allelic discrimination assay, we genotyped a total of 1080 patients undergoing coronary angiography. This population contained 3 groups of patients: controls with atypical chest pain, abnormal stress testing but normal coronary angiography (n = 154), patients with angina who underwent uncomplicated primary coronary intervention (n = 230), and patients with acute MI (n = 696). In MI patients, left ventricular ejection fraction (LVEF) was determined 1-month after MI with echocardiography., Results: The frequency of the CCR5delta32 deletion was 16.3% in the global population, and was similar between controls, patients with angina and MI patients. The deletion was not associated with variations of plasma levels of creatine phosphokinase and troponin T, nor it was associated with LVEF, New York Heart Association class or 2-year mortality. The frequency of the deletion was comparable between MI patients with LV dysfunction (EF < or = 40%, n = 82) and no LV dysfunction (EF > 40%, n = 402)., Conclusions: The frequency of the CCR5delta32 deletion in Luxembourg is similar to that observed in other European countries and is not associated with the risk of developing MI and LV dysfunction.

The national LUCKY registry (Luxembourg Acute Myocardial Infarction Registry) confirms for Luxembourg that transfer of patients with acute myocardial infarction for primary percutaneous coronary intervention (PCI) is very effective. However, while mortality is low after PCI, a third of the patients with acute myocardial infarction develop severe left ventricular dysfunction. This may in part be explained by relatively long time delays between onset of symptoms and opening of the infarct-related artery, despite short distances between hospitals (time is myocardium). Surprisingly, in comparison with men, women are younger, have a higher body mass index and receive less evidence-based therapies such as statins before and after myocardial infarction. In conclusion, PCI has substantially improved the treatment of acute myocardial infarction in Luxembourg, but all actors including the patient have to keep efforts high to minimize time delays.