Ahmed Ibrahim

Pericardial Fat Is Independently Associated With Human Atrial Fibrillation

OBJECTIVES The purpose of this study was to investigate the association between atrial fibrillation (AF) and pericardial fat. BACKGROUND Pericardial fat is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with AF, but the relationship between AF and pericardial fat is unknown. METHODS Pericardial fat volume was measured using computed tomography in 273 patients: 76 patients in sinus rhythm, 126 patients with paroxysmal AF, and 71 patients with persistent AF. RESULTS Patients with AF had significantly more pericardial fat compared with patients in sinus rhythm (101.6 +/- 44.1 ml vs. 76.1 +/- 36.3 ml, p < 0.001). Pericardial fat volume was significantly larger in paroxysmal AF compared with the sinus rhythm group (93.9 +/- 39.1 ml vs. 76.1 +/- 36.3 ml, p = 0.02). Persistent AF patients had a significantly larger pericardial fat volume compared with paroxysmal AF (115.4 +/- 49.3 ml vs. 93.9 +/- 39.1 ml, p = 0.001). Pericardial fat volume was associated with paroxysmal AF (odds ratio: 1.11; 95% confidence interval: 1.01 to 1.23, p = 0.04) and persistent AF (odds ratio: 1.18, 95% confidence interval: 1.05 to 1.33, p = 0.004), and this association was completely independent of age, hypertension, sex, left atrial enlargement, valvular heart disease, left ventricular ejection fraction, diabetes mellitus, and body mass index. CONCLUSIONS Pericardial fat volume is highly associated with paroxysmal and persistent AF independent of traditional risk factors including left atrial enlargement. Whether pericardial fat plays a role in the pathogenesis of AF requires future investigation.

Exosomes: Fundamental Biology and Roles in Cardiovascular Physiology.

Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell. The information within exosomes prominently includes their protein and RNA payloads. Exosomal microRNAs in particular can potently and fundamentally alter the transcriptome of recipient cells. Here we summarize what is known about exosome biogenesis, content, and transmission, with a focus on cardiovascular physiology and pathophysiology. We also highlight some of the questions currently under active investigation regarding these extracellular membrane vesicles and their potential in diagnostic and therapeutic applications.

Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion

Cardiosphere‐derived cells (CDCs) reduce myocardial infarct size via secreted extracellular vesicles (CDC‐EVs), including exosomes, which alter macrophage polarization. We questioned whether short non‐coding RNA species of unknown function within CDC‐EVs contribute to cardioprotection. The most abundant RNA species in CDC‐EVs is a Y RNA fragment (EV‐YF1); its relative abundance in CDC‐EVs correlates with CDC potency in vivo. Fluorescently labeled EV‐YF1 is actively transferred from CDCs to target macrophages via CDC‐EVs. Direct transfection of macrophages with EV‐YF1 induced transcription and secretion of IL‐10. When cocultured with rat cardiomyocytes, EV‐YF1‐primed macrophages were potently cytoprotective toward oxidatively stressed cardiomyocytes through induction of IL‐10. In vivo, intracoronary injection of EV‐YF1 following ischemia/reperfusion reduced infarct size. A fragment of Y RNA, highly enriched in CDC‐EVs, alters Il10 gene expression and enhances IL‐10 protein secretion. The demonstration that EV‐YF1 confers cardioprotection highlights the potential importance of diverse exosomal contents of unknown function, above and beyond the usual suspects (e.g., microRNAs and proteins).

A comprehensive method for identification of suitable reference genes in extracellular vesicles

ABSTRACT Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) is one of the most sensitive, economical and widely used methods for evaluating gene expression. However, the utility of this method continues to be undermined by a number of challenges including normalization using appropriate reference genes. The need to develop tailored and effective strategies is further underscored by the burgeoning field of extracellular vesicle (EV) biology. EVs contain unique signatures of small RNAs including microRNAs (miRs). In this study we develop and validate a comprehensive strategy for identifying highly stable reference genes in a therapeutically relevant cell type, cardiosphere-derived cells. Data were analysed using the four major approaches for reference gene evaluation: NormFinder, GeNorm, BestKeeper and the Delta Ct method. The weighted geometric mean of all of these methods was obtained for the final ranking. Analysis of RNA sequencing identified miR-101-3p, miR-23a-3p and a previously identified EV reference gene, miR-26a-5p. Analysis of a chip-based method (NanoString) identified miR-23a, miR-217 and miR-379 as stable candidates. RT-qPCR validation revealed that the mean of miR-23a-3p, miR-101-3p and miR-26a-5p was the most stable normalization strategy. Here, we demonstrate that a comprehensive approach of a diverse data set of conditions using multiple algorithms reliably identifies stable reference genes which will increase the utility of gene expression evaluation of therapeutically relevant EVs.

ABNORMAL GLOBAL LONGITUDINAL STRAIN PREDICTS ADVERSE CARDIAC EVENTS IN SARCOIDOSIS

In patients with systemic sarcoidosis (CS), myocardial involvement is often analyzed by echocardiography and positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET). However, global longitudinal strain (GLS) may be the earliest sign of myocardial involvement. We sought to compare GLS with