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Cardioprotective effect of 5-lipoxygenase gene [ALOX5] silencing in ischemia-reperfusion

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Lisovyy O. O., Dosenko V. E., Nagibin V. S., Tumanovska L. V., Korol M. O., Surova O. V., Moibenko O. O.

Acta Biochimica Polonica

2009

tom 56

nr 4

687-694

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 LTC4 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.

Ograniczanie wyników

1 Acta Biochimica Polonica

1 Dosenko V. E.

1 Korol M. O.

1 Lisovyy O. O.

1 Moibenko O. O.

1 Nagibin V. S.

1 Surova O. V.

1 Tumanovska L. V.

1 2009

Wyniki wyszukiwania

Cardioprotective effect of 5-lipoxygenase gene [ALOX5] silencing in ischemia-reperfusion