© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Eicosapentanoic acid inhibits hypoxia-reoxygenation-induced injury by attenuating upregulation of MMP-1 in adult rat myocytes
aDepartment of Medicine, University of Arkansas for Medical Science and Central Arkansas Veterans Health Care System, Little Rock, AR, USA
bDepartment of Physiology and Biophysics, University of Arkansas for Medical Science, Little Rock, AR, USA
cDepartment of Forensic Medicine, University of Uppsala, Uppsala, Sweden
mehtajl{at}uams.edu
* Corresponding author. Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, 4301 West Markham, #532, Little Rock, AR 72205-7199, USA. Tel.: +1-501-296-1401; fax: +1-501-686-6180.
Background: Myocardial hypoxia-reoxygenation (H-R) is associated with upregulation of metalloproteinases (MMPs). Upregulation of MMPs is associated with cell injury. Previous studies have shown that fish oil can protect myocardium from injury induced by H-R. This study was designed to examine the effect of eicosapentanoic acid (EPA), one of the major components in fish oil, on the modulation of MMP-1 expression in response to H-R in cultured adult rat myocytes. Methods and results: Myocytes isolated from adult Sprague–Dawley rat hearts were cultured with or without EPA or arachidonic acid (AA) (10 and 50 µM) and exposed to 24 h of hypoxia followed by 3 h of reoxygenation (H-R). H-R resulted in myocyte injury (measured on LDH release), increase in p38MAPK phosphorylation (Western analysis), augmentation of lipid peroxidation, and upregulation of MMP-1 activity (zymography) and expression (RT-PCR and Western analysis) (all P<0.01 vs. control, n = 5). Pretreatment of myocytes with EPA, but not AA, resulted in a reduction in LDH release, and attenuation of p38MAPK phosphorylation and MMP-1 activity and expression in response to H-R (all P<0.05 vs. H-R alone). Pretreatment of myocytes with EPA also reduced lipid peroxidation in myocytes exposed to H-R (P<0.05 vs. H-R alone). A high concentration of EPA (50 µM) was more potent than the lower concentration of EPA (10 µM). Conclusions: These observations suggest that EPA attenuates an increase in MMP-1 following H-R, which may be a basis of protection of myocytes from the adverse effects of H-R. p38MAPK phosphorylation may be an important signaling event in this process.
KEYWORDS EPA; Arachidonic acid; Hypoxia-reoxygenation; MAP kinase; MMP-1; Myocytes
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