Cardioprotective effect of 5-lipoxygenase gene (ALOX5) silencing in ischemia-reperfusion.

Oleksandr O Lisovyy; Victor E Dosenko; Vasyl S Nagibin; Lesya V Tumanovska; Maria O Korol; Olga V Surova; Olexiy O Moibenko

doi:10.18388/abp.2009_2503

Cardioprotective effect of 5-lipoxygenase gene (ALOX5) silencing in ischemia-reperfusion.

Oleksandr O Lisovyy Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kiev, Ukraine.;
Victor E Dosenko
Vasyl S Nagibin
Lesya V Tumanovska
Maria O Korol
Olga V Surova
Olexiy O Moibenko

DOI: https://doi.org/10.18388/abp.2009_2503

Abstract

It is well known that 5-lipoxygenase derivates of arachidonic acid play an important pathogenic role during myocardial infarction. Therefore, the gene encoding arachidonate 5-lipoxygenase (ALOX5) appears to be an attractive target for RNA interference (RNAi) application. In experiments on cultivated cardiomyocytes with anoxia-reoxygenation (AR) and in vivo using rat model of heart ischemia-reperfusion (IR) we determined influence of ALOX5 silencing on myocardial cell death. ALOX5 silencing was quantified using real-time PCR, semi-quantitative PCR, and evaluation of LTC(4) concentration in cardiac tissue. A 4.7-fold decrease of ALOX5 expression (P < 0.05) was observed in isolated cardiomyocytes together with a reduced number of necrotic cardiomyocytes (P < 0.05), increased number live (P < 0.05) and unchanged number of apoptotic cells during AR of cardiomyocytes. Downregulation of ALOX5 expression in myocardial tissue by 19% (P < 0.05) resulted in a 3.8-fold reduction of infarct size in an open chest rat model of heart IR (P < 0.05). Thus, RNAi targeting of ALOX5 protects heart cells against IR injury both in culture and in vivo.

Published

2009-12-11

Issue

Vol. 56 No. 4 (2009)

Section

Articles

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