Matrix metalloproteinase activity expression in infarcted, noninfarcted and dilated cardiomyopathic human hearts
Matrix metalloproteinase activity expression in infarcted, noninfarcted and dilated cardiomyopathic human hearts
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DOI：
10.1007/bf00714328
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发表时间：
1996-02-09
影响因子：
4.3
通讯作者：
Voelker, DJ
中科院分区：
文献类型：
--
作者：
Tyagi, SC;Campbell, SE;Voelker, DJ
在正常心肌中，基质金属蛋白酶（MMP）以潜在形式存在。为了检查 MMP 是否在梗塞或特发性扩张型心肌病 (DCM) 后被激活，我们提取并测量了 7 个因既往心肌梗塞 (MI) 或 DCM 导致衰竭的人类心脏外植心脏组织中的 MMP 活性。将 MI 患者的梗死左心室 (LV)、非梗死 LV 和右心室 (RV) 以及 DCM 患者任一心室的组织中的 MMP 活性与供体心脏组织的活性进行比较。 SDS-PAGE 和染料结合测定用于确定总蛋白浓度，而胶原酶活性则通过嵌入 I 型明胶的 SDS-PAGE 型底物凝胶来测量（酶谱法）。对于小至 0.05 mg 的组织样品，酶谱技术的准确度与分光光度法获得的结果相当。总蛋白浓度标准化后，我们发现正常心房组织中胶原酶活性为 3 +/- 1%，可被胰蛋白酶或纤溶酶激活至 80-90%，表明胶原酶在人心脏中通常不活跃或处于潜伏状态。另一方面，在梗塞左心室的心内膜和心外膜中，胶原酶活性分别为 85-95% 和 10-20%，而在非梗塞左心室中，胶原酶活性分别为 5-10% 和 3-5%。在DCM中，左心室的内膜和外膜的溶胶原活性分别为75 +/- 5%和35 +/- 5%，右心室的溶胶原活性分别为35 rt 7和20 +/- 5%。因此，在继发于既往 MI 或 DCM 的扩张性衰竭人类心脏中，MMP 活性增加。在患有 MI 的任一心室的梗塞和非梗塞部分的心内膜心肌内以及在 DCM 的两个心室中尤其如此。这表明整个心肌中胶原酶的激活可能有助于其重塑，包括心室扩张和壁变薄。
In the normal myocardium matrix metalloproteinases (MMP) are present in the latent form. To examine whether MMP are activated following infarction or idiopathic dilated cardiomyopathy (DCM), we extracted and measured MMP activity in tissue derived from 7 explanted, failing human hearts due to either previous myocardial infarction (MI) or DCM. MMP activity in infarcted left ventricle (LV), noninfarcted LV and right ventricle (RV) from MI patients, as well as tissue from either ventricle of DCM patients, were compared to the activity of donor heart tissue. SDS-PAGE and dye-binding assays were used to determine total protein concentration, while collagenase activity was measured by SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Accuracy of the zymographic technique was shown for tissue samples as small as 0.05 mg and was comparable to results obtained by a spectrophotometric method. After normalization for total protein concentration, we found 3 +/- 1% collagenase activity in normal atrial tissue which could be activated to 80-90% by trypsin or plasmin, indicating that collagenase is normally inactive or in a latent form in human heart. In endo- and epimyocardium of infarcted LV, on the other hand, collagenase activity was 85-95% and 10-20%, respectively, while 5-10% and 3-5%, respectively, in noninfarcted LV. In DCM, collagenolytic activity in the endo and epimyocardium was 75 +/- 5 and 35 +/- 5% in the LV and 35 rt 7 and 20 +/- 5% in the RV, respectively. Thus, in dilated failing human hearts secondary to previous MI or DCM, MMP activity is increased. This is particularly the case within the endomyocardium of the infarcted and noninfarcted portions of either ventricle with MI and in both ventricles in DCM. This suggests that an activation of collagenase throughout the myocardium may contribute to its remodeling that includes ventricular dilatation and wall thinning.