Poster Session
Event Title
Date
May 2017
Document Type
Poster Abstract
Description
Introduction: The majority of new atrial fibrillation (AF) cases occur in elderly patients with cardiac remodeling (CR) in the setting of structural heart disease and heart failure (HF). We leveraged a unique animal model to identify cardiac microRNAs (miRNAs) and gene regulatory mechanisms that drive this process.
Methods: We prospectively quantified atrial expression of 48 miRNAs by high-throughput qRT-PCR in 15 pigs with right-atrial pacing-induced heart disease (5 pigs with AF/severe HF, 5 pigs with AF/mild HF, and 5 control pigs) as well as in 21 patients (11 with AF and CR and 10 controls) undergoing cardiac surgery. CR and HF were defined through a metric of left atrial volume index, BNP and ejection fraction. MiRNA levels were normalized to global mean and expression compared across pig subtypes and between the two human groups.
Results: In the porcine model, miR-208b was upregulated at week 1 (ΔCT= -3.9, pT = -5.5, pT = -1.5, pT = -1.5, p<0.05) after induction of AF compared to sinus rhythm animals. The increase persisted at week 3 compared to week 1 (ΔCT = -1.5, p<0.05). Similarly, humans with AF and HF had higher tissue expression of miR-208b compared to controls (ΔCT = -1.5, p<0.05).
Conclusions: Dysregulation of miR-208b is confirmed in our porcine model and is validated in humans. Prior studies have identified miR-208b in both myosin isoform switching and conduction disease. We theorize that dysregulation of miR-208b may play a critical role in atrial structural remodeling and vulnerability to AF.
Keywords
cardiac remodeling, atrial fibrillation, heart failure
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Transcriptional Regulation of Cardiac Remodeling in a Porcine Model with Validation in Human Subjects
Introduction: The majority of new atrial fibrillation (AF) cases occur in elderly patients with cardiac remodeling (CR) in the setting of structural heart disease and heart failure (HF). We leveraged a unique animal model to identify cardiac microRNAs (miRNAs) and gene regulatory mechanisms that drive this process.
Methods: We prospectively quantified atrial expression of 48 miRNAs by high-throughput qRT-PCR in 15 pigs with right-atrial pacing-induced heart disease (5 pigs with AF/severe HF, 5 pigs with AF/mild HF, and 5 control pigs) as well as in 21 patients (11 with AF and CR and 10 controls) undergoing cardiac surgery. CR and HF were defined through a metric of left atrial volume index, BNP and ejection fraction. MiRNA levels were normalized to global mean and expression compared across pig subtypes and between the two human groups.
Results: In the porcine model, miR-208b was upregulated at week 1 (ΔCT= -3.9, pT = -5.5, pT = -1.5, pT = -1.5, p<0.05) after induction of AF compared to sinus rhythm animals. The increase persisted at week 3 compared to week 1 (ΔCT = -1.5, p<0.05). Similarly, humans with AF and HF had higher tissue expression of miR-208b compared to controls (ΔCT = -1.5, p<0.05).
Conclusions: Dysregulation of miR-208b is confirmed in our porcine model and is validated in humans. Prior studies have identified miR-208b in both myosin isoform switching and conduction disease. We theorize that dysregulation of miR-208b may play a critical role in atrial structural remodeling and vulnerability to AF.