Nicotinamide-rich diet protects the heart against ischaemia-reperfusion in mice: a crucial role for cardiac SUR2A.
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 cardioprotection 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.
Sukhodub
Andriy
A
Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK.
Du
Qingyou
Q
Jovanović
Sofija
S
Jovanović
Aleksandar
A
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D054086:KATP Channels / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000178:diet therapy* / Q000517:prevention & control*; D009536:Niacinamide / Q000627:therapeutic use*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; C577511:Abcc9 protein, mouse; D002316:Cardiotonic Agents; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D009536:Niacinamide