Author + information
- Hyelim Parka,b,
- Hyoeun Kima,b,
- Hyewon Parka,b,
- Shanyu Cuia,b,
- Hui-Nam Paka,b,
- Moon-Hyoung Leea,b and
- Boyoung Jounga,b
Background: Exosome contains and delivers bioactive molecults critical to intracellular signaling. However, the role and mechanism of exosome which regulates molecular interactions in atrial fibrillation (AF) was not revealed. This study evaluated whether exosome from AF patients can effect electrical and structural remodeling in pacing induced tachycardia model.
Methods: Exosome was isolated from plasma of AF patients. The HL-1 atrial cardiomyocytes were divided into three group; normal paced (1 Hz, NP), tachy-paced (5Hz, TP), tachy-paced with control exosome (TP + CoExo) and tachy-paced with exosome from AF patient (TP + AFExo) group. In the TP + Exo group, HL-1 cells were treated with the exosome for 24 hours before pacing. The effects of exosome on TP HL-1 cells were examined using a patch clamp, a confocal Ca2+ imaging, immunoblotting and immunofluorescence staining. To identify valuable targets for heart defects, microarray were used to obtain miRNA expression profiles from control and TP exosome.
Results: Tachypacing of HL-1 atrial cardiomyocytes significantly impaired contractile function. This dysfunction was prevented by exosome isolated from AF patients and tubacin. Tachy-pacing induced shortening of action potential duration, loss of Ca2+ transient amplitude and depolymerization of microtubules through Histone Deacetylase-6 (HDAC-6). However, these dyfunction induced tachypacing were significantly preveted by AFExo pretreatment, but not CoExo. Let-7i miRNA level was significantly increased in exosomes derived from AF patients, which was rescued by suppressing HDAC6 expression and led to electrical and structural remodeling.
Conclusions: AF induces remodeling and loss of contractile function in part through HDAC6 and subsequent derailment of α-tubulin proteostasis and disruption of the cardiomyocyte microtubule structure. Exosome from atrial fibrillation protects against AF-related atrial remodeling, disclosing the potential of HDAC6 as a therapeutic target in clinical AF.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: Arrhythmias and Clinical EP: Basic 1
Abstract Category: 4. Arrhythmias and Clinical EP: Basic
Presentation Number: 1107-072
- 2017 American College of Cardiology Foundation