Haptoglobin genotype determines myocardial infarct size in diabetic mice
Haptoglobin genotype determines myocardial infarct size in diabetic mice
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DOI：
10.1016/j.jacc.2006.08.044
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发表时间：
2007-01-02
影响因子：
24
通讯作者：
Levy, Andrew P.
中科院分区：
文献类型：
--
作者：
Blum, Shany;Asaf, Roy;Levy, Andrew P.
目的我们试图了解氧化应激在解释为什么触珠蛋白（Hp）基因型决定糖尿病（DM）心肌梗死（MI）的大小的重要性。背景两个常见的等位基因（I和2）存在于人类Hp基因座。Hp 2等位基因与糖尿病患者心肌梗死面积增加相关.在体外实验中，Hp 2蛋白与氧化活性铁的产生增加有关，而Hp I蛋白与抗氧化细胞因子白细胞介素（IL）10的产生增加有关。方法用携带Hp I或Hp 2等位基因的DM C57 BL/6小鼠，通过心肌缺血再灌注（IR）造成心肌梗死。采用电喷雾质谱法评估IR后心肌氧化应激。IR后测定血清中的氧化还原活性铁和IL-10。结果与Hp I小鼠相比，Hp 2小鼠的心肌梗死面积显著更大（44.3 +/- 9.3%对21.0 +/-4.0%，p = 0.03），这些较大的梗死与一组羟基-二十碳四烯酸的显著增加有关。氧化还原活性铁在Hp 2小鼠中更高（0.45 +/- 0.11 μ mol/l vs. 0.14 +/- 0.05 μ mol/l，p = 0.02），而IL-10在Hp I小鼠中更高（85.8 +/- 12.9 pg/mu l vs. 46.7 +/- 10.8 pg/mu l，p = 0.04）。（BXT-51072）对Hp 2小鼠的IR后心肌损伤减少80%以上（p = 0.003），结论DM Hp 2小鼠IR后心肌梗死面积增加可能与DM Hp 2小鼠IR后心肌梗死面积增加有关，增加氧化应激。(c)2007年美国心脏病学会基金会
Objectives We sought to understand the importance of oxidative stress in explaining why the haptoglobin (Hp) genotype determines myocardial infarction (MI) size in diabetes mellitus (DM).Background Two common alleles (I and 2) exist at the Hp locus in humans. The Hp 2 allele is associated with increased MI size in individuals with DM. In vitro, the Hp 2 protein is associated with increased generation of oxidatively active iron, whereas the Hp I protein is associated with increased production of the antioxidant cytokine interleukin (IL)-10.Methods Myocardial infarction was produced by myocardial ischemia-reperfusion (IR) in DM C57BL/6 mice carrying the Hp I or Hp 2 allele. Myocardial oxidative stress after IR was assessed using electrospray ionization mass spectrometry. Redox active iron and IL-10 were measured in the serum after IR.Results Myocardial infarction size was significantly larger in Hp 2 mice as compared with Hp I mice (44.3 +/- 9.3% vs. 21.0 +/- 4.0%, p = 0.03), and these larger infarctions were associated with a significant increase in a panel of hydroxyl-eicosatetraenoic acids. Redox active iron was greater in Hp 2 mice (0.45 +/- 0.11 mu mol/l vs. 0.14 +/- 0.05 mu mol/l, p = 0.02), whereas IL-10 was greater in Hp I mice (85.8 +/- 12.9 pg/mu l vs. 46.7 +/- 10.8 pg/mu l, p = 0.04) after IR. Administration of an antioxidant (BXT-51072) to Hp 2 mice reduced myocardial injury after IR by more than 80% (p = 0.003), but no myocardial protection was provided by the antioxidant to Hp 1 mice.Conclusions The increased MI size in DM Hp 2 mice occurring after IR may be due to increased oxidative stress. (c) 2007 by the American College of Cardiology Foundation