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

100%
Lisovyy O., Dosenko V., Nagibin V., Tumanovska L., Korol M., Surova O., Moibenko O.
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issue 4
687-694
EN
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.
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Wpływ melatoniny na czynność układu sercowo-naczyniowego

63%
Sewerynek E.
Folia Medica Lodziensia
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2010
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vol. 37
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issue 1
69-87
EN
The ageing process is associated with an increasing number of cardiovascular incidents, both acute and chronic. Also the concentrations of certain hormones undergo a gradual decrease with age, including: oestrogens, androgens, dehydroepiandrosterone, dehydroapiandrosterone sulphate or melatonin. The association between melatonin and circulation has been the subject of interest for the last few years. It has also been demonstrated that the vasospastic or vasodilative effects of melatonin depend on the activation of certain receptors by the hormone. Cardioprotective effects of melatonin have been demonstrated in both experimental and clinical studies. In cardiac ischemia-reperfusion models or in the course of oxidative process induction, following the administration of medical agents with cardiotoxic effects, protective effects of melatonin have been demonstrated. In patients with ischaemic heart disease, lower nocturnal melatonin concentrations were found vs. those in a group of healthy persons; the more severe cardiac disease and the higher risk for sudden cardiac death, the lower melatonin concentrations are observed. Lower melatonin concentrations have also been confirmed in patients with hypercholesteronaemia and increased LDL-cholesterol fraction levels, as well as in patients with arterial hypertension. Melatonin administration normalised blood pressure in patients with arterial hypertension. The presented paper aims at summarising the up-to-date knowledge of the role of melatonin in circulation control.
PL
melatonin. The association between melatonin and circulation has been the subject of interest for the last few years. It has also been demonstrated that the vasospastic or vasodilative effects of melatonin depend on the activation of certain receptors by the hormone. Cardioprotective effects of melatonin have been demonstrated in both experimental and clinical studies. In cardiac ischemia-reperfusion models or in the course of oxidative process induction, following the administration of medical agents with cardiotoxic effects, protective effects of melatonin have been demonstrated. In patients with ischaemic heart disease, lower nocturnal melatonin concentrations were found vs. those in a group of healthy persons; the more severe cardiac disease and the higher risk for sudden cardiac death, the lower melatonin concentrations are observed. Lower melatonin concentrations have also been confirmed in patients with hypercholesteronaemia and increased LDL-cholesterol fraction levels, as well as in patients with arterial hypertension. Melatonin administration normalised blood pressure in patients with arterial hypertension. The presented paper aims at summarising the up-to-date knowledge of the role of melatonin in circulation control.
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