Cardioprotective effect of 5-lipoxygenase gene (ALOX5) silencing in ischemia-reperfusion.
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.
Lisovyy
Oleksandr O
OO
Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Dosenko
Victor E
VE
Nagibin
Vasyl S
VS
Tumanovska
Lesya V
LV
Korol
Maria O
MO
Surova
Olga V
OV
Moibenko
Olexiy O
OO
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D016923:Cell Death; D020868:Gene Silencing; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar
D001094:Arachidonate 5-Lipoxygenase