Angiotensin-receptor blockade reduces border zone myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration in post-infarction ventricular remodeling
Angiotensin-receptor blockade reduces border zone myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration in post-infarction ventricular remodeling
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DOI：
10.1253/circj.cj-08-0115
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发表时间：
2008-10-01
影响因子：
3.3
通讯作者：
Ogawa, Satoshi
中科院分区：
文献类型：
--
作者：
Kohno, Takashi;Anzai, Toshihisa;Ogawa, Satoshi
背景单核细胞趋化蛋白-1（MCP-1）是心肌梗死（MI）早期左心室（LV）重塑的关键介质。该假设测试是，心肌MCP-1的表达将增加在慢性阶段的MI和血管紧张素II型1受体阻滞剂（ARB）将减弱巨噬细胞浸润，通过减少心肌MCP-1expression.Methods和结果MI是由结扎左冠状动脉在Wistar大鼠，然后被随机处理与车辆（MI/C），坎地沙坦（10 mg.kg（-1）.day（-1））6周（MI/ARB 0 - 6 W），或坎地沙坦2周，开始4周后MI（MI/ARB 4 - 6 W）。MI后6周，MI/ARB 0 - 6 W组的左室收缩压和舒张末期压较MI/C或MI/ARB 4 - 6 W组降低，但其他血流动力学或超声心动图参数在梗死大鼠组间无差异。ARB的长期和短期治疗同样降低了MCP-1和转化生长因子-31的mRNA表达。结论在MI后心力衰竭中，ARB可降低边缘区MCP-1表达和巨噬细胞浸润。导致较少的心肌巨噬细胞相关炎症。
Background Monocyte chernoattractant protein-1 (MCP-1) is a key mediator of left ventricular (LV) remodeling during the early phase of myocardial infarction (MI). The hypothesis tested was that myocardial MCP-1 expression would increase during the chronic phase of MI and in angiotensin-II type 1 receptor blocker (ARB) would attenuate macrophage infiltration through decreased myocardial MCP-1 expression.Methods and Results MI was produced by ligation of the left coronary artery in Wistar rats, which were then randomized to treatment with vehicle (MI/C), candesartan (10 mg.kg(-1).day(-1)) for 6 weeks (MI/ARB0-6W), or candesartan for 2 weeks, starting 4 weeks after MI (MI/ARB4-6W). LV systolic and end-diastolic pressures 6 weeks after MI were decreased in MI/ARB0-6W compared with MI/C or MI/ARB4-6W, however, there were no differences in other hemodynamic or echocardiographic parameters among infarcted rat groups. Both long- and short-term treatments with ARB similarly reduced mRNA expressions of MCP-1, transforming growth factor-31. and procollagen type I and III, macrophage infiltration, and myocardial fibrosis in the border zone.Conclusions In post-MI heart failure, ARB attenuated MCP-1 expression and macrophage infiltration in the border zone. resulting in less myocardial macrophage-related inflammation.