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Cardiovascular Research 2005 66(1):74-83; doi:10.1016/j.cardiores.2004.12.009
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Copyright © 2004, European Society of Cardiology

Oxidized LDL induces ventricular myocyte damage and abnormal electrical activity–role of lipid hydroperoxides

Klaus Zorn-Paulya, Peter Schaffera,*, Brigitte Pelzmanna, Eva Bernharta, Guofeng Weib,c, Petra Langa, Gerhard Ledinskib, Joachim Greilbergerb, Bernd Koidla and Günther Jürgensb

aCenter of Physiological Medicine, Institute of Biophysics, Medical University Graz, Harrachgasse 21/4, A-8010 Graz, Austria
bCenter of Physiological Medicine, Institute of Physiological Chemistry, Medical University Graz, Graz, Austria
cDepartment of Cardiology, 2nd Hospital of Dalian Medical University, Dalian, PR China

* Corresponding author. Tel.: +43 316 385 72027; fax: +43 316 385 72034. Email address: peter.schaffer{at}meduni-graz.at

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 °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.

KEYWORDS Lipoproteins; Oxygen radicals; Repolarization; Membrane currents; Ion channels


Time for primary review 26 days


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