Cardiac remodeling by fibrous tissue after infarction in rats
Cardiac remodeling by fibrous tissue after infarction in rats
复制标题
DOI：
10.1067/mlc.2000.105971
复制
发表时间：
2000-04-01
期刊：
影响因子：
--
通讯作者：
Lamparter, S
中科院分区：
文献类型：
--
作者：
Sun, Y;Zhang, JQ;Lamparter, S
透壁性心肌梗死（MI）后，梗死区和非梗死区心肌均出现广泛的纤维组织重构，导致心室舒张功能障碍。在本研究中，我们试图通过检测左冠状动脉结扎后2至28天与胶原合成和降解相关的空间和时间依赖性细胞事件来评估梗死大鼠心脏胶原重塑的时间过程。结果表明：（1）心肌梗死后第2天，巨噬细胞浸润于心肌梗死和心包脏层，第14天后逐渐消失，（2）心肌修复后第3天，心肌成纤维细胞（Myofibroblasts，MyoFb）开始出现，此后各时间点均大量存在;（3）转化生长因子-β（4）I型和III型胶原mRNA在MI后第3天开始增加，此后持续升高;（5）心肌梗死时及梗死后第3天MMP-1 mRNA显著升高，第7天降至对照组水平，此后一直维持低水平;（6）基质金属蛋白酶组织抑制剂（TIMP）-Ⅰ、-Ⅱ和-Ⅲ mRNA在第3天修复部位显著升高，并持续28天;（7）在第7天在MI时和远离MI时明显的纤维状胶原积累此后在每个部位持续积累4周。与未手术的车辙心脏相比，梗死和非梗死心脏的心包纤维化明显，心包胶原生成/降解的时间反应与心肌梗死相似。因此，前壁梗死后，梗死和非梗死大鼠心肌胶原合成均被激活，并持续28小时;而早期胶原降解是短暂的，并且在纤维化阶段是失活的。活化的TGF-β 1 mRNA表达伴随着MyoFb的出现以及纤维胶原和TIMP的表达，表明这种纤维化细胞因子可能有助于MI后大鼠心脏中的胶原重塑。
After transmural myocardial infarction (MI), extensive myocardial remodeling by fibrous tissue appears in both infarcted and noninfarcted myocardium, which contributes to ventricular diastolic dysfunction. In the present study we sought to assess the time course of collagen remodeling in the infarcted rat hearts by detecting spatial and time-dependent cellular events related to collagen synthesis and degradation 2 to 28 days after left coronary artery ligation. In infarcted hearts, and compared with findings in sham-operated and unoperated rat hearts, we found the following: (1) macrophages infiltrated into sites of MI and visceral pericardium on day 2 and gradually disappeared after day 14; (2) myofibroblasts (MyoFb) first appeared at these sites of repair on day 3 and remained abundant thereafter at all time points examined; (3) transforming growth factor-beta (TGF-beta 1) mRNA was enhanced in infarcted and noninfarcted myocardium on day 2 and remained throughout 28 days; (4) type I and III collagen mRNAs began to increase at and remote to Mi on day 3 and remained elevated thereafter; (5) matrix metalloproteinase-1 mRNA was significantly increased at and remote to MI on day 3, declined to the control level on day 7, and remained low thereafter; (6) tissue inhibitor of matrix metalloproteinase (TIMP)-I, -II, and -III mRNAs were markedly elevated at sites of repair on day 3 and sustained throughout 28 days; (7) fibrillar collagen accumulation that was evident at and remote to MI on day 7 continued to accumulate thereafter at each site over 4 weeks. When compared with findings in unoperated rut heart, pericardial fibrosis was evident In both infarcted and noninfarcted heart, and the temporal response of collagen generation/ degradation in pericardium was similar to that in Infarcted myocardium, Thus collagen synthesis is activated in both infarcted and noninfarcted rat myocardium after transmural anterior infarction and Is persistent throughout the 28;day period of study whereas early collagen degradation is short lived and inactivated in the fibrogenic phase. Activated TGF-beta 1 mRNA expression is accompanied by the appearance of MyoFb and the expression of fibrillar collagens and TIMPs, suggesting that this fibrogenic cytokine may contribute to collagen remodeling in the rat heart after MI.