A role for decorin in the remodeling of myocardial infarction
A role for decorin in the remodeling of myocardial infarction
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DOI：
10.1016/j.matbio.2005.05.003
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发表时间：
2005-06-01
期刊：
影响因子：
6.9
通讯作者：
McCulloch, AD
中科院分区：
文献类型：
--
作者：
Weis, SM;Zimmerman, SD;McCulloch, AD
由于富含亮氨酸的小蛋白聚糖核心蛋白聚糖与胶原纤维生成的调节有关，从而导致适当的细胞外基质组装，因此我们假设它可能在心肌梗塞后的心脏纤维化中发挥关键作用。在这项研究中，我们结扎了野生型和核心蛋白聚糖磨小鼠的左冠状动脉前降支，以在左心室前壁产生大的梗塞。在冠状动脉闭塞后的早期阶段：两种基因型之间的心肌梗塞大小没有明显差异。然而，我们发现在核心蛋白聚糖缺失小鼠的成熟疤痕中，胶原纤维尺寸分布更广泛，组织较少且包装松散。因此，我们测试了以下假设：这些异常的胶原纤维会对梗塞后力学和心室重塑产生不利影响。事实上，急性心肌梗死后 14 天，与野生型同窝动物相比，核心蛋白聚糖工厂动物的疤痕大小、右心室远端肥大和左心室扩张更大。超声心动图显示核心蛋白聚糖工厂动物缺血后 4 至 8 周左心室收缩功能下降。这些变化表明核心蛋白聚糖是心肌梗塞正常纤维化进展所必需的，并且它的缺失会导致异常疤痕组织的形成。这可能导致动脉瘤性心室扩张、远端肥厚和心室功能下降。 (c) 2005 年 Elsevier B.V./国际基质生物学学会。版权所有。
Because the small leucine-rich proteoglycan decorin has been implicated in regulation of collagen fibrillogenesis leading to proper extracellular matrix assembly, we hypothesized it could play a key role in cardiac fibrosis following myocardial infarction. In this study we ligated the left anterior descending coronary artery in wildtype and decorin-mill mice to produce large infarcts in the anterior wall of the left ventricle. At early stages post-coronary occlusion the: myocardial infarction size did not appreciably differ between the two genotypes. However, we found a wider distribution of collagen fibril sizes with less organization and loose packing in mature scar from decorin-null mice. Thus, we tested the hypothesis that these abnormal collagen fibrils would adversely affect post-infarction mechanics and ventricular remodeling. Indeed, scar size, right ventricular remote hypertrophy, and left ventricular dilatation were greater in decorin-mill animals compared with wildtype littermates 14 days after acute myocardial infarction. Echocardiography revealed depressed left ventricular systolic function between 4 and 8 weeks post-ischemia in the decorin-mill animals. These changes indicate that decorin is required for the proper fibrotic evolution of myocardial infarctions, and that its absence leads to abnormal scar tissue formation. This might contribute to aneurysmal ventricular dilatation, remote hypertrophy, and depressed ventricular function. (c) 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved.