Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction
Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction
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DOI：
10.1161/01.atv.0000193567.88685.f4
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发表时间：
2006-01-01
影响因子：
8.7
通讯作者：
Hansson, GK
中科院分区：
文献类型：
--
作者：
Hemdahl, AL;Gabrielsen, A;Hansson, GK
目的：中性粒细胞明胶酶相关脂钙蛋白(NGAL)调节基质金属蛋白酶9(MMP9)的活性，MMP9是动脉粥样硬化中血管重构和斑块不稳定性的重要介质。本研究旨在分析NGAL在动脉粥样硬化斑块和心肌梗死(MI)中的表达。方法和结果：动脉粥样硬化性载脂蛋白E(ApoE)(-/-)x低密度脂蛋白受体(LDLR)(-/-)和C57BL/6J对照组小鼠暴露于短暂低氧应激(10分钟10%氧气)。48小时后用定量RT-PCR、免疫组织化学和酶图谱分析小鼠NGAL同源物(24p3)和基质金属蛋白酶-9的表达。低氧应激使心脏血管中NGAL/24p3mRNA表达增加。与C57BL/6J小鼠相比，载脂蛋白E-/-x LDLR-/-小鼠动脉粥样硬化斑块中NGAL/24p3的表达也增加。心肌梗死小鼠的NGAL/24p3和MMP-9斑块mRNA表达水平最高。凝胶电泳图显示在富含24p3和基质金属蛋白酶-9蛋白的区域有很强的蛋白分解活性。对人颈动脉内膜切除标本和乳内动脉对照组织进行免疫组织化学染色发现，在动脉粥样硬化斑块中，基质金属蛋白酶-9和NGAL与巨噬细胞共存。结论：NGAL/24p3在动脉粥样硬化斑块和心肌梗死中表达增加。在蛋白分解活性较高的区域与基质金属蛋白酶-9共定位，提示NGAL/24p3在调节基质金属蛋白酶-9介导的斑块和梗死心脏重塑中发挥作用。
Objective: Neutrophil gelatinase-associated lipocalin (NGAL) modulates the activity of matrix metalloproteinase (MMP) 9, an important mediator of vascular remodeling and plaque instability in atherosclerosis. This study aimed to analyze the expression of NGAL in atherosclerotic plaques and myocardial infarction (MI).Methods and Results: Atherosclerotic apolipoprotein E (apoE)(-/-) x low-density lipoprotein receptor (LDLR)(-/-) and C57BL/6J control mice were exposed to brief hypoxic stress (10 minutes of 10% oxygen). Expression of the mouse NGAL homolog (24p3) and MMP-9 was analyzed 48 hours later by quantitative RT-PCR, immunohistochemistry, and zymography. Hypoxic stress increased NGAL/24p3 mRNA in the cardiac vasculature. NGAL/24p3 was also increased in atherosclerotic plaques of apolipoprotein E-/- x LDLR-/- mice compared with C57BL/6J mice. Mice developing MI exhibited the highest plaque mRNA expression of NGAL/24p3 and MMP-9. Zymography revealed strong proteolytic activity in areas rich in 24p3 and MMP-9 protein. Immunohistochemistry performed on human carotid endarterectomy specimens and control tissue from the internal mammary artery showed colocalization of MMP-9 and NGAL with macrophages in the atherosclerotic plaques.Conclusions: NGAL/24p3 is increased in atherosclerotic plaques and MI. Colocalization with MMP-9 in areas with high-proteolytic activity suggests a role for NGAL/24p3 in modulating the MMP-9-mediated remodeling of plaques and infarcted hearts.