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心脏移植中的基质金属蛋白酶及其组织抑制剂

Matrix metalloproteases and their tissue inhibitor in cardiac transplantation.

作者信息

Aharinejad Seyedhossein, Krenn Katharina, Zuckermann Andreas, Schäfer Romana, Paulus Patrick, Seebacher Gernot, Wolner Ernst, Grimm Michael

机构信息

Department of Cardiothoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

出版信息

Eur J Cardiothorac Surg. 2007 Jul;32(1):48-51. doi: 10.1016/j.ejcts.2007.04.007. Epub 2007 May 4.

DOI:10.1016/j.ejcts.2007.04.007
PMID:17482473
Abstract

OBJECTIVE

Multiple studies have shown that matrix metalloproteases (MMPs) are involved in the pathologic reactions occurring as a consequence of cardiac transplantation, including ischemia-reperfusion injury and allograft rejection. This study sought to determine the temporal profile of MMP serum levels following cardiac transplantation.

METHODS

Endomyocardial biopsies and serum samples were obtained from 66 recipients at 1, 2, 3, 4, 7, 12, 24, and 52 weeks post-transplant during the routine follow-up protocol, and MMP-1, MMP-8, MMP-9, and tissue inhibitor of metalloproteases (TIMP)-1 serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Immunosuppression comprised cyclosporine A (CyA; n=46) or tacrolimus (TAC; n=20) with mycophenolate mofetil and steroids.

RESULTS

Increased MMP-8, MMP-9, and TIMP-1 serum levels were observed during the first 2 weeks following transplantation compared to the later time points. MMP-1 was increased at 2 and 3 weeks post-transplant compared to all later time points. No correlation of MMP or TIMP serum concentrations with infection episodes was observed.

CONCLUSIONS

Early increase in MMP and TIMP serum levels following cardiac transplantation indicates involvement of these molecules in the reaction of the transplant to ischemia-reperfusion or early immunologic adaptation processes of the host. Further investigation of the relationship between MMP and TIMP serum levels and clinical conditions following transplantation including allograft rejection and hemodynamic graft function is necessary.

摘要

目的

多项研究表明,基质金属蛋白酶(MMPs)参与心脏移植后发生的病理反应,包括缺血再灌注损伤和同种异体移植排斥反应。本研究旨在确定心脏移植后MMP血清水平的时间变化情况。

方法

在常规随访方案中,于移植后1、2、3、4、7、12、24和52周从66例受者获取心内膜心肌活检组织和血清样本,采用酶联免疫吸附测定(ELISA)法检测MMP-1、MMP-8、MMP-9和金属蛋白酶组织抑制剂(TIMP)-1的血清浓度。免疫抑制方案包括环孢素A(CyA;n = 46)或他克莫司(TAC;n = 20)联合霉酚酸酯和类固醇。

结果

与后期时间点相比,移植后前2周观察到MMP-8、MMP-9和TIMP-1血清水平升高。与所有后期时间点相比,MMP-1在移植后2周和3周升高。未观察到MMP或TIMP血清浓度与感染发作之间的相关性。

结论

心脏移植后MMP和TIMP血清水平早期升高表明这些分子参与移植对缺血再灌注的反应或宿主的早期免疫适应过程。有必要进一步研究移植后MMP和TIMP血清水平与包括同种异体移植排斥反应和移植血流动力学功能在内的临床状况之间的关系。

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