Nicotinamide-rich diet protects the heart against ischaemia-reperfusion in mice: A crucial role for cardiac SUR2A

Andriy Sukhodub, Qingyou Du, Sofija Jovanovic, Aleksandar Jovanovic

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    Abstract

    It is a consensus view that a strategy to increase heart resistance to ischaemia-reperfusion is a warranted. Here, based on our previous study, we have hypothesized that a nicotinamide-rich diet could increase myocardial resistance to ischaemia-reperfusion. Therefore, the purpose of this study was to determine whether nicotinamide-rich diet would increase heart resistance to ischaemia-reperfusion and what is the underlying mechanism. Experiments have been done on mice on control and nicotinamide-rich diet (mice were a week on nicotinamide-rich diet) as well as on transgenic mice overexpressing SUR2A (SUR2A mice), a regulatory subunit of cardioprotective ATP-sensitive K+ (K-ATP) channels and their littermate controls (WT). The levels of mRNA in heart tissue were measured by real-time RT-PCR, whole heart and single cell resistance to ischaemia-reperfusion and severe hypoxia was measured by TTC staining and laser confocal microscopy, respectively. Nicotinamide-rich diet significantly decreased the size of myocardial infarction induced by ischaemia-reperfusion (from 42.5 +/- 4.6% of the area at risk zone in mice on control diet to 26.8 +/- 1.8% in mice on nicotinamide-rich diet, n = 6-12, P= 0.031). The cardioprotective effect of nicotinamide-rich diet was associated with 11.46 +/- 1.22 times (n = 6) increased mRNA levels of SUR2A in the heart. HMR1098, a selective inhibitor of the sarcolemmal K-ATP channels opening, abolished cardio-protection afforded by nicotinamide-rich diet. Transgenic mice with a sole increase in SUR2A expression had also increased cardiac resistance to ischaemia-reperfusion. We conclude that nicotinamide-rich diet up-regulate SUR2A and increases heart resistance to ischaemia-reperfusion. (C) 2010 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)564-570
    Number of pages7
    JournalPharmacological Research
    Volume61
    Issue number6
    DOIs
    Publication statusPublished - Jun 2010

    Keywords

    • Nicotinamide
    • Ischaemia
    • SUR2A
    • KATP
    • channels
    • SENSITIVE K+ CHANNELS
    • ATP CHANNELS
    • H9C2 CELLS
    • M-LDH
    • CARDIOMYOCYTES
    • KINASE
    • TRAFFICKING
    • MYOCARDIUM
    • EXPRESSION
    • MECHANISM

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