Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction
Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction
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DOI：
10.1161/circulationaha.107.749234
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发表时间：
2008-02-26
期刊：
影响因子：
37.8
通讯作者：
Mantovani, Alberto
中科院分区：
文献类型：
--
作者：
Salio, Monica;Chimenti, Stefano;Mantovani, Alberto
背景--尽管临床上广泛使用短五聚蛋白作为缺血性心脏病的预后标志物，但由于小鼠和人类之间的进化差异，短五聚蛋白C-反应蛋白的实际致病作用尚未经过严格的基因检测。长五聚蛋白PTX 3在进化中是保守的，在炎症条件下在心脏中表达，并且是急性心肌梗死的候选预后标志物。因此，重要的是要评估是否PTX 3在急性心肌infarction.Methods和结果-在冠状动脉结扎和再灌注引起的急性心肌梗死模型中发挥致病作用，组织mRNA表达和循环水平的PTX 3增加。IL-1 R-MyD 88通路在缺血后诱导PTX 3转录中起关键作用。ptx 3缺陷型小鼠表现出加重的心脏损伤（在无效小鼠中，梗塞面积增大33%; P = 0.0047）。ptx 3缺陷小鼠心肌损伤增加与无复流面积增大、中性粒细胞浸润增加、毛细血管数量减少和凋亡心肌细胞数量增加相关。此外，ptx 3基因缺陷小鼠急性心肌梗死表现出较高的循环水平的白细胞介素-6和增加C3沉积在病变组织。外源性PTX 3可逆转上述表型。结论：PTX 3在小鼠急性心肌梗死中起着非冗余的、调节性的心脏保护作用。我们的研究结果表明，补体级联的调制有助于PTX 3的心脏保护功能。
Background- Despite widespread clinical use as a prognostic marker in ischemic heart disorders, the actual pathogenetic role of the short pentraxin, C-reactive protein, has not undergone stringent genetic testing because of evolutionary divergence between mouse and humans. The long pentraxin PTX3 is conserved in evolution, is expressed in the heart under inflammatory conditions, and is a candidate prognostic marker in acute myocardial infarction. It was therefore important to assess whether PTX3 plays a pathogenetic role in acute myocardial infarction.Methods and Results- In a model of acute myocardial infarction caused by coronary artery ligation and reperfusion, tissue mRNA expression and circulating levels of PTX3 increased. The interleukin-1R-MyD88 pathway plays a pivotal role in the induction of PTX3 transcript after ischemia. ptx3-deficient mice showed exacerbated heart damage (33% larger infarcts in null mice; P = 0.0047). Increased myocardial damage in ptx3-deficient mice was associated with a greater no-reflow area, increased neutrophil infiltration, decreased number of capillaries, and increased number of apoptotic cardiomyocytes. In addition, ptx3-deficient mice with acute myocardial infarction showed higher circulating levels of interleukin-6 and increased C3 deposition in lesional tissue. The phenotype was reversed by exogenous PTX3.Conclusions- Thus, PTX3 plays a nonredundant, regulatory, cardioprotective role in acute myocardial infarction in mice. Our results suggest that modulation of the complement cascade contributes to the cardioprotective function of PTX3.