Targeted deletion of CC chemokine receptor 2 attenuates left ventricular remodeling after experimental myocardial infarction
Targeted deletion of CC chemokine receptor 2 attenuates left ventricular remodeling after experimental myocardial infarction
复制标题
DOI：
10.1016/s0002-9440(10)63309-3
复制
发表时间：
2004-08-01
影响因子：
6
通讯作者：
Takeya, M
中科院分区：
文献类型：
--
作者：
Kaikita, K;Hayasaki, T;Takeya, M
急性心肌梗死（MI）后心脏重塑的一个关键组成部分是炎症反应，它调节心脏组织修复。本研究的目的是探讨单核细胞炎症反应和左心室重构心肌梗死后使用小鼠缺乏CC趋化因子受体2（CCR 2），CC趋化因子配体2的关键调节剂的主要受体之间的关系。免疫组织化学分析显示，在野生型（WT）小鼠中，巨噬细胞在7天内迅速浸润到梗死组织中。然而，这一过程在CCR 2缺陷（CCR 2（-/-））小鼠中受到极大损害。超声心动图显示心肌梗死后第7天和第28天CCR 2缺陷对左心室重构有有益影响。原位酶谱显示MI后7天内WT小鼠的明胶分解活性增强，而CCR 2（-/-）小鼠的明胶分解活性几乎检测不到。此外，明胶分解活性在连续切片中的分布与巨噬细胞而不是中性粒细胞的分布非常相似。MI后3天，WT小鼠梗死区基质金属蛋白酶和肿瘤坏死因子-α mRNA的表达较CCR 2（-/-）小鼠上调。直接抑制心肌梗死后CCR 2功能通路可能有助于减轻心肌梗死后左室重构。
A key component of cardiac remodeling after acute myocardial infarction (MI) is the inflammatory response, which modulates cardiac tissue repair. The purpose of this study was to investigate the relationship between the monocytic inflammatory response and left ventricular remodeling after MI using mice deficient in CC chemokine receptor 2 (CCR2), the primary receptor for the critical regulator of CC chemokine ligand 2. Immunohistochemical analysis revealed rapid infiltration of macrophages; into infarcted tissue within 7 days in wild-type (WT) mice. However, this process was greatly impaired in CCR2-deficient (CCR2(-/-)) mice. Echocardiography demonstrated beneficial effects of CCR2 deficiency on left ventricular remodeling at 7 and 28 days after MI. In situ zymography showed augmented gelatinolytic activity in WT mice within 7 days after MI, whereas gelatinolytic activity was barely detectable in CCR2(-/-) mice. Moreover, the distribution of gelatinolytic activity in serial sections was very similar to the distribution of macrophages rather than neutrophils. Expression of matrix metalloproteinases and tumor necrosis factor-alpha mRNAs was up-regulated in infarcted regions from WT mice compared to CCR2(-/-) mice at 3 days after MI. Direct inhibition of CCR2 functional pathway might contribute to the attenuation of left ventricular remodeling after MI.