Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite
Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite
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DOI：
10.1152/ajpheart.00484.2009
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发表时间：
2009-11-01
影响因子：
4.8
通讯作者：
Ferdinandy, Peter
中科院分区：
文献类型：
--
作者：
Kupai, Krisztina;Csonka, Csaba;Ferdinandy, Peter
Kupai K, Csonka C, Fekete V, Odendaal L, van Rooyen J, Marais DW, Csont T, Ferdinandy P.高胆固醇饮食诱导的高脂血症对心脏保护作用的影响。[J] .中国生物医学工程学报，2009,31(2):555 - 557。2009年9月4日首次发表；doi: 10.1152 / ajpheart.00484.2009。本研究的目的是研究高脂血症是否会干扰后处理的梗死面积限制作用，并研究过氧亚硝酸盐在这一现象中的作用。给大鼠喂食富含2%胆固醇的食物或正常饮食12周。对两组分离的心脏进行30分钟冠状动脉闭塞，然后再灌注120分钟（有或没有后处理方案，在再灌注开始时进行10秒冠状动脉闭塞和10秒再灌注的6个周期），用氯化三苯四唑染色测量梗死面积。在正常血脂组，后处理显著降低梗死面积，而在高血脂组则没有。3-硝基酪氨酸浓度（过氧亚硝酸盐形成的标志）在再灌注第5分钟测量时在正常组增加，而在胆固醇喂养组没有增加。接下来，我们在单独的实验中测试了后适应诱导的过氧亚硝酸盐急性增加是否参与正常血脂动物的心脏保护。在正常血脂动物中，后处理不能减少过氧亚硝酸盐分解催化剂5,10,15,20-四-[4-磺酰基]-卟啉铁[III] （20mg /l）的梗死面积。我们得出结论，后处理后过氧亚硝酸盐的早期增加在心脏保护中起作用。此外，高脂血症至少在一定程度上通过后适应诱导的过氧亚硝酸盐形成早期增加的恶化，阻断了后适应的心脏保护作用。
Kupai K, Csonka C, Fekete V, Odendaal L, van Rooyen J, Marais DW, Csont T, Ferdinandy P. Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite. Am J Physiol Heart Circ Physiol 297: H1729-H1735, 2009. First published September 4, 2009; doi:10.1152/ajpheart.00484.2009.-The aim of the present study was to investigate if hyperlipidemia interferes with the infarct size-limiting effect of postconditioning and to study the involvement of peroxynitrite in this phenomenon. Rats were fed a 2% cholesterol-enriched or normal diet for 12 wk. Infarct size by triphenyltetrazolium chloride staining was measured in hearts isolated from both groups and subjected to 30 min coronary occlusion followed by 120 min reperfusion with or without the postconditioning protocol induced by six cycles of 10 s coronary occlusion and 10 s reperfusion at the onset of the reperfusion. Postconditioning significantly decreased infarct size in the normolipidemic but not in the hyperlipidemic group. Postconditioning increased cardiac 3-nitrotyrosine concentration (a marker for peroxynitrite formation) in the normal but not in the cholesterol-fed group when measured at the 5th min of reperfusion. Next, we tested if the postconditioning-induced acute increase in peroxynitrite is involved in the cardioprotection in normolipidemic animals in separate experiments. Postconditioning failed to decrease infarct size in the presence of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron [III] (20 mg/l) in normolipidemic animals. We conclude that an early increase in peroxynitrite after postconditioning plays a role in cardioprotection. Furthermore, hyperlipidemia blocks the cardioprotective effect of postconditioning at least in part via deterioration of the postconditioning-induced early increase in peroxynitrite formation.