REGULATION OF COLLAGEN DEGRADATION IN THE RAT MYOCARDIUM AFTER INFARCTION
REGULATION OF COLLAGEN DEGRADATION IN THE RAT MYOCARDIUM AFTER INFARCTION
复制标题
DOI：
10.1016/s0022-2828(05)82390-9
复制
发表时间：
1995-06-01
影响因子：
5
通讯作者：
WEBER, KT
中科院分区：
文献类型：
--
作者：
CLEUTJENS, JPM;KANDALA, JC;WEBER, KT
基质金属蛋白酶（MMP-1）降解维持心肌结构完整性所必需的原纤维胶原。在其他组织中，胶原溶解是伤口愈合的重要组成部分。在这里，我们研究了心肌梗死后胶原蛋白的降解。采用酶谱法测定大鼠左冠状动脉结扎后6 h ~ 28 d心肌胶原酶活性，北方印迹法和原位杂交法检测心肌基质金属蛋白酶1（MMP-1）和金属蛋白酶组织抑制剂（TIMP）mRNA的表达。将梗塞左心室与非梗塞右心室、室间隔和假手术组织进行比较，我们发现梗塞左心室胶原酶活性在第2天开始短暂增加（与对照组相比增加4.5倍），在第7天达到峰值（6.5倍增长），此后下降，以及明胶酶（MMP-2和MMP-9）的胶原溶解活性的伴随增加和贡献。胶原酶mRNA的增加，直到第7天，只有在梗死的心室，而MMP-1的活性或mRNA表达的变化没有观察到在远程网站或假手术对照。TIMP mRNA的转录在6小时（增加两倍），在心肌梗死后第2天达到峰值（增加8倍），此后缓慢下降。在远处或假手术对照中未观察到TIMP mRNA表达的变化。负责MMP-1和TIMP mRNA转录的细胞是成纤维细胞样细胞，而不是炎性细胞或内皮细胞。在梗死部位，潜在胶原酶（MMP-1）的翻译后激活在伤口愈合反应中起着比胶原酶mRNA转录更大的作用。当MMP-1的潜在细胞外池通过潜在胶原酶和明胶酶的活化而减少时，合成胶原酶mRNA。TIMP mRNA的合成受MMP活化的调节，胶原酶活化和TIMP抑制之间的平衡决定了梗死组织中胶原溶解的量。
Fibrillar collagens, essential for maintaining the structural integrity of the myocardium, are degraded by matrix metalloproteinase (MMP-1), In other tissues collagenolysis is an important component of wound healing. Here we examined collagen degradation in the myocardium after infarction. Collagenase activity, measured by zymography, and expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of metalloproteinase (TIMP) mRNA, detected by Northern blotting and in situ hybridization, in the rat heart 6 h to 28 days after left coronary artery ligation were studied, Sham-operated rats served as controls. Infarcted left ventricle was compared to noninfarcted right ventricle and interventricular septum and to sham-operated tissues, We found a transient increase in collagenase activity in the infarcted left ventricle, which began at day 2 (4.5-fold increase compared to controls), peaked at day seven (6.5-fold increase) and declined thereafter, together with a concomitant increase and contribution in collagenolytic activity of gelatinases (MMP-2 and MMP-9). An increase in collagenase mRNA was not seen until day 7 and only in the infarcted ventricle, while changes in MMP-1 activity or mRNA expression were not observed at remote sites or in sham-operated controls. Transcription of TIMP mRNA was observed at 6 h (two-fold increase) in the infarcted ventricle, peaked on day two after MI (eight-fold increase) and slowly decreased thereafter. No change In TIMP mRNA expression was observed at remote sites or in sham-operated controls. Cells responsible for transcription of MMP-1 and TIMP mRNA were fibroblast-like cells, not inflammatory or endothelial cells. At the site of infarction post-translational activation of latent collagenase (MMP-1) plays a greater role in the wound healing response than transcription of collagenase mRNA. Collagenase mRNA is synthesized when the latent extracellular pool of MMP-1 is reduced through the activation of latent collagenases and gelatinases. TIMP mRNA synthesis is regulated by the activation of MMPs with the balance between collagenase activation and TIMP inhibition determining the amount of collagenolysis in infarcted tissue.