Fig. 7
Summary and putative mechanism of action of C18:1AC. Elevated serum concentrations of the long-chain acyl-carnitine C18:1AC were identified to be associated with incident and prevalent atrial fibrillation (AF), and a the arrhythmogenic potential of C18:1AC was experimentally assessed using different in vitro models. b Our experiments support the idea that the bipolar metabolite C18:1AC can interact with cellular membranes and thereby influences associated receptors and ion channels. We propose that C18:1AC concentrations can increase intracellular Ca2+ concentration which induces a positive inotropic effect (1) but also arrhythmic events (2, illustrated as irregular contraction peaks). C18:1AC evoked a biphasic effect on mitochondrial respiration (3) characterised by stimulation at lower and inhibition at higher concentrations. Based on our identification of an impaired C18:1AC metabolism in patients with sustained AF, we hypothesise that long-chain ACs contribute to the maintenance of AF as follows: Reduced oxygen supply during AF results in impaired mitochondrial β-oxidation leading to accumulation of long-chain ACs, which in turn affects mitochondrial metabolism and contractility further. We suggest that long-time exposure to high C18:1AC concentrations, for instance during ischemic conditions, results in progressive cellular accumulation of the metabolite and consequently rather non-specific effects like impaired cardiac contractility (4). ATP adenosine triphosphate, KC Krebs cycle, SR sarcoplasmic reticulum