Human electronegative low-density lipoprotein modulates cardiac repolarization via LOX-1-mediated alteration of sarcolemmal ion channels

Dyslipidemia is associated with greater risk of ventricular tachyarrhythmias in patients with cardiovascular diseases. We aimed to examine whether the most electronegative subfraction of low-density lipoprotein (LDL), L5, is correlated with QTc prolongation in patients with coronary artery disease (...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-09, Vol.7 (1), p.10889-14, Article 10889
Main Authors: Lee, An-Sheng, Xi, Yutao, Lai, Chin-Hu, Chen, Wei-Yu, Peng, Hsien-Yu, Chan, Hua-Chen, Chen, Chu-Huang, Chang, Kuan-Cheng
Format: Article
Language:English
Subjects:
Action potential
Angiography
Calcium
Calcium channels (L-type)
Cardiomyocytes
Cardiovascular disease
Cardiovascular diseases
Coronary artery
Coronary artery disease
Dyslipidemia
Heart diseases
Ion channels
Ischemia
Low density lipoprotein
LOX-1 protein
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Dyslipidemia is associated with greater risk of ventricular tachyarrhythmias in patients with cardiovascular diseases. We aimed to examine whether the most electronegative subfraction of low-density lipoprotein (LDL), L5, is correlated with QTc prolongation in patients with coronary artery disease (CAD) and investigate the effects of human L5 on the electrophysiological properties of cardiomyocytes in relation to the lectin-like oxidized LDL receptor (LOX-1). L5 was isolated from the plasma of 40 patients with angiography documented CAD and 13 patients with no CAD to correlate the QTc interval respectively. The mean concentration of L5 was higher and correlated with QTc in patients with CAD compared to controls. To examine the direct effect of L5 on QTc, mice were intravenously injected with L5 or L1. L5-injected wild-type but not LOX-1 mice showed longer QTc compared to L1-injected animals in vivo with corresponding longer action potential duration (APD) in cardiomyocytes incubated with L5 in vitro. The APD prolongation was mediated by an increase of L-type calcium current and a decrease of transient outward potassium current. We show that L5 was positively correlated with QTc prolongation in patients with ischemic heart disease. L5 can modulate cardiac repolarization via LOX-1-mediated alteration sarcolemmal ionic currents.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-10503-x