Human electronegative low-density lipoprotein modulates cardiac repolarization via LOX-1-mediated alteration of sarcolemmal ion channels
- Resource Type
- Authors
- An-Sheng Lee; Wei-Yu Chen; Yutao Xi; Chu-Huang Chen; Hsien-Yu Peng; Chin-Hu Lai; Hua-Chen Chan; Kuan-Cheng Chang
- Source
- Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
Scientific Reports
- Subject
- 0301 basic medicine
medicine.medical_specialty
Action Potentials
lcsh:Medicine
Coronary Artery Disease
030204 cardiovascular system & hematology
QT interval
Ion Channels
Article
Coronary artery disease
Mice
03 medical and health sciences
Sarcolemma
0302 clinical medicine
In vivo
Internal medicine
medicine
Animals
Humans
Myocyte
Myocytes, Cardiac
cardiovascular diseases
Scavenger receptor
lcsh:Science
Cells, Cultured
Multidisciplinary
business.industry
Myocardium
lcsh:R
Scavenger Receptors, Class E
medicine.disease
Cardiovascular physiology
Lipoproteins, LDL
030104 developmental biology
Endocrinology
Cardiology
cardiovascular system
lcsh:Q
business
Dyslipidemia
Lipoprotein
- Language
- English
- ISSN
- 2045-2322
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.