Oxidized LDL induces ventricular myocyte damage and abnormal electrical activity--role of lipid hydroperoxides.
OBJECTIVE
It was our aim to investigate effects of human LDL, copper-, or AAPH-oxidized over different periods of time to different degrees (ox-LDL), on viability and electrophysiological parameters of isolated ventricular myocytes of guinea pigs.


METHODS
Guinea pig ventricular myocytes were incubated with ox-LDL or native LDL (at 0.5 mg/ml) for 12 h, and afterwards myocyte damage, action potentials, and transmembrane ion currents were studied (at 37 degrees C).


RESULTS
Ox-LDL was found to induce severe myocyte damage, whereas native LDL had no effect. Myocyte damage was dependent on the content of total lipid hydroperoxides in both copper-oxidized and AAPH-oxidized LDL. Incubation with ox-LDL led to intense contractile and electrophysiological effects including prolongation of action potential duration, depolarization of resting membrane potential, spontaneous activity, generation of afterdepolarizations, and modification of transmembrane ion currents (e.g. inward rectifier, calcium, and background currents).


CONCLUSIONS
Ox-LDL induced cell damage and irregular electrical activity in ventricular myocytes. These effects were dependent on the lipid hydroperoxide content of ox-LDL and were similar to oxidative stress (OS) induced by various OS-generating systems. The observed effects may play a role for functional cardiac abnormalities in patients with increased ox-LDL levels.
Zorn-Pauly
Klaus
K
Center of Physiological Medicine, Institute of Biophysics, Medical University Graz, Harrachgasse 21/4, A-8010 Graz, Austria.
Schaffer
Peter
P
Pelzmann
Brigitte
B
Bernhart
Eva
E
Wei
Guofeng
G
Lang
Petra
P
Ledinski
Gerhard
G
Greilberger
Joachim
J
Koidl
Bernd
B
Jürgens
Günther
G
D000200:Action Potentials / Q000187:drug effects*; D000328:Adult; D000578:Amidines / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D018929:Cell Culture Techniques; D002470:Cell Survival; D003300:Copper / Q000378:metabolism; D006168:Guinea Pigs; D006352:Heart Ventricles; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects
D000578:Amidines; D015220:Calcium Channels; D007473:Ion Channels; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D024661:Potassium Channels, Inwardly Rectifying; C099252:oxidized low density lipoprotein; C046728:2,2'-azobis(2-amidinopropane); D003300:Copper