Long-Chain Acylcarnitines and Cardiac Excitation-Contraction Coupling: Links to Arrhythmias
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Long-Chain Acylcarnitines and Cardiac Excitation-Contraction Coupling: Links to Arrhythmias. / Aitken-Buck, Hamish M.; Krause, Julia; Zeller, Tanja; Jones, Peter P.; Lamberts, Regis R.
in: FRONT PHYSIOL, Jahrgang 11, 577856, 11.09.2020.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - Long-Chain Acylcarnitines and Cardiac Excitation-Contraction Coupling: Links to Arrhythmias
AU - Aitken-Buck, Hamish M.
AU - Krause, Julia
AU - Zeller, Tanja
AU - Jones, Peter P.
AU - Lamberts, Regis R.
N1 - Publisher Copyright: © Copyright © 2020 Aitken-Buck, Krause, Zeller, Jones and Lamberts.
PY - 2020/9/11
Y1 - 2020/9/11
N2 - A growing number of metabolomic studies have associated high circulating levels of the amphiphilic fatty acid metabolites, long-chain acylcarnitines (LCACs), with cardiovascular disease (CVD) risk. These studies show that plasma LCAC levels can be correlated with the stage and severity of CVD and with indices of cardiac hypertrophy and ventricular function. Complementing these recent clinical associations is an extensive body of basic research that stems mostly from the twentieth century. These works, performed in cardiomyocyte and multicellular preparations from animal and cell models, highlight stereotypical derangements in cardiac electrophysiology induced by exogenous LCAC treatment that promote arrhythmic muscle behavior. In many cases, this is coupled with acute inotropic modulation; however, whether LCACs increase or decrease contractility is inconclusive. Linked to the electromechanical alterations induced by LCAC exposure is an array of effects on cardiac excitation-contraction coupling mechanisms that overload the cardiomyocyte cytosol with Na+ and Ca2+ ions. The aim of this review is to revisit this age-old literature and collate it with recent findings to provide a pathophysiological context for the growing body of metabolomic association studies that link circulating LCACs with CVD.
AB - A growing number of metabolomic studies have associated high circulating levels of the amphiphilic fatty acid metabolites, long-chain acylcarnitines (LCACs), with cardiovascular disease (CVD) risk. These studies show that plasma LCAC levels can be correlated with the stage and severity of CVD and with indices of cardiac hypertrophy and ventricular function. Complementing these recent clinical associations is an extensive body of basic research that stems mostly from the twentieth century. These works, performed in cardiomyocyte and multicellular preparations from animal and cell models, highlight stereotypical derangements in cardiac electrophysiology induced by exogenous LCAC treatment that promote arrhythmic muscle behavior. In many cases, this is coupled with acute inotropic modulation; however, whether LCACs increase or decrease contractility is inconclusive. Linked to the electromechanical alterations induced by LCAC exposure is an array of effects on cardiac excitation-contraction coupling mechanisms that overload the cardiomyocyte cytosol with Na+ and Ca2+ ions. The aim of this review is to revisit this age-old literature and collate it with recent findings to provide a pathophysiological context for the growing body of metabolomic association studies that link circulating LCACs with CVD.
KW - arrhythmias
KW - calcium
KW - cardiac pathophysiology
KW - electrophysiology
KW - excitation-contraction coupling
KW - long-chain acylcarnitines
KW - metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85091576819&partnerID=8YFLogxK
U2 - 10.3389/fphys.2020.577856
DO - 10.3389/fphys.2020.577856
M3 - SCORING: Review article
AN - SCOPUS:85091576819
VL - 11
JO - FRONT PHYSIOL
JF - FRONT PHYSIOL
SN - 1664-042X
M1 - 577856
ER -