van den Borne Susanne W M, Cleutjens Jack P M, Hanemaaijer Roeland, Creemers Esther E, Smits Jos F M, Daemen Mat J A P, Blankesteijn W Matthijs
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Cardiovasc Pathol. 2009 Jan-Feb;18(1):37-43. doi: 10.1016/j.carpath.2007.12.012. Epub 2008 Mar 4.
Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an important role in infarct rupture. The present study was designed to study the role of MMP-2, MMP-8, and MMP-9 in human infarct rupture.
Heart samples were obtained from patients who died from infarct rupture and control MI patients. The MMP activity was determined by zymography and quantitative immunocapture activity assay. TIMP-1 levels were measured and immunohistochemistry for MMP-2 and MMP-9 was performed.
The amounts of both total and active MMP-8 and MMP-9 were significantly higher in ruptured infarct tissue than in control MI tissue, but no differences in MMP-2 activity were observed. Furthermore, the number of inflammatory cells was significantly higher in the ruptured infarcts than in control infarcts.
These data suggest that increased MMP-8 and MMP-9 activity in the infarct area, caused by a more prominent infiltration of inflammatory cells, contribute to infarct rupture in humans.
梗死破裂是心肌梗死（MI）常见的致命并发症，目前尚未明确其在人类中的分子机制。小鼠模型实验证据表明，基质金属蛋白酶（MMPs）介导的细胞外基质降解在梗死破裂中起重要作用。本研究旨在探讨MMP - 2、MMP - 8和MMP - 9在人类梗死破裂中的作用。
收集因梗死破裂死亡患者及对照MI患者的心脏样本。通过酶谱法和定量免疫捕获活性测定法测定MMP活性。检测组织金属蛋白酶抑制剂 - 1（TIMP - 1）水平，并对MMP - 2和MMP - 9进行免疫组织化学检测。
梗死破裂组织中总MMP - 8和MMP - 9以及活性MMP - 8和MMP - 9的含量均显著高于对照MI组织，但未观察到MMP - 2活性存在差异。此外，梗死破裂处的炎性细胞数量显著高于对照梗死。
这些数据表明，炎性细胞浸润更为显著导致梗死区域MMP - 8和MMP - 9活性增加，这在人类梗死破裂中起作用。
