Targeted deletion of class A macrophage scavenger receptor increases the risk of cardiac rupture after experimental myocardial infarction
Targeted deletion of class A macrophage scavenger receptor increases the risk of cardiac rupture after experimental myocardial infarction
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DOI：
10.1161/circulationaha.106.671198
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发表时间：
2007-04-10
期刊：
影响因子：
37.8
通讯作者：
Takeya, Motohiro
中科院分区：
文献类型：
--
作者：
Tsujita, Kenichi;Kaikita, Koichi;Takeya, Motohiro
背景-A类巨噬细胞清道夫受体（SR-A）是一种巨噬细胞限制性多功能分子，通过调节炎性细胞因子的活性来优化炎症反应。本研究是用SR-A缺陷（SR-A（-/-））小鼠来评估SR-A和心肌梗塞后心脏重构之间的关系。方法和结果-通过结扎SR-A（-/-）和野生型（WT）雄性小鼠的左冠状动脉来产生实验性心肌梗塞（MI）。MI后4周内死亡的小鼠数量在SR-A（-/-）小鼠中显著高于WT小鼠（P = 0.03）。重要的是，MI后1周内心脏破裂导致的死亡在SR-A（-/-）小鼠中为31%（54只小鼠中的17只），在WT小鼠中为12%（51只小鼠中的6只）（P = 0.01）。原位酶谱显示SR-A（-/-）小鼠与WT小鼠相比，梗死心肌中明胶分解活性增强。实时荧光定量逆转录聚合酶链反应（RT-PCR）结果显示，与WT小鼠相比，SR-A（-/-）小鼠梗死心肌中基质金属蛋白酶-9mRNA的表达明显增加。此外，SR-A（-/-）小鼠在MI后第3天显示梗死心肌中肿瘤坏死因子-α的表达增加和白细胞介素-10的减少。体外实验也证明了增加的肿瘤坏死因子-α和减少的白细胞介素-10在激活SR-A（-/-）macrophage.Conclusions表达-目前的研究结果表明，SR-A缺乏可能会导致损害梗死重塑，导致心脏破裂，通过生产不足的白细胞介素-10和增强表达的肿瘤坏死因子-α和基质金属蛋白酶-9。SR-A可能有助于预防MI后心脏破裂。
Background - Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A-deficient (SR-A(-/-)) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction.Methods and Results - Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A(-/-) and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A(-/-) mice than in WT mice (P = 0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A(-/-) mice and 12% (6 of 51 mice) in WT mice (P = 0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Real-time reverse transcription - polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Furthermore, SR-A(-/-) mice showed augmented expression of tumor necrosis factor-alpha and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-alpha and decreased interleukin-10 expression in activated SR-A(-/-) macrophages.Conclusions - The present findings suggest that SR- A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor-alpha and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.