MMP-7、MMP-10和TIMP-4在心力衰竭心室重构中的表达

目的:应用细胞因子抗体芯片技术筛选与心力衰竭心室重构关系密切的基质蛋白酶。方法:从本院的心脏病组织库中挑选6例病理诊断明确和各方面资料比较齐全的致心律失常性右室心肌病引起心力衰竭的心脏病标本(来源于心脏移植的受体)，与年龄、性别和种族等因素相匹配的正常对照心脏组织(来源于心脏移植的供体)进行细胞因子抗体芯片分析，筛选在致心律失常性右室心肌病引起的心力衰竭中差异表达的基质蛋白酶，并应用酶联免疫分析和免疫组织化学的方法加以验证。结果:在所筛选的17种基质金属蛋白酶中，只有MMP-7和MMP-10在致心律失常性右室心肌病引起心力衰竭中高表达，而在4种基质金属蛋白酶内源性组织抑制剂中，只有TIMP-4 低表达。经酶联免疫分析和免疫组织化学的方法证实，不仅在致心律失常性右室心肌病引起心力衰竭的心肌，在缺血性心肌病和扩张性心肌病引起的心力衰竭心肌中也发现MMP-7和MMP-10 的高表达及TIMP-4的低表达。结论:心肌组织中MMP-7和MMP-10的高表达及TIMP-4的低表达在不同心肌病引起的心力衰竭心室重构分子机制中可能发挥重要的作用。

MMP-7,MMP-10 and TIMP-4 expression in ventricular remodeling of human heart failure

AIM:To sieve matrix metalloproteinases (MMPs) and the tissue inhibitors of matrix metalloproteinases (TIMPs) closely associated with ventricular remodeling of human heart failure using antibody chip technology.METHODS:We performed cytokine-specific antibody array analysis using individual left ventricular myocardial samples from 6 patients with heart failure due to arrythmogenic right ventricular cardiomyopathy (ARVC) undergoing transplantation and matched samples from 6 non-failing subjects to screen differentially expressed MMPs and TIMPs associated with the ventricular remodeling of heart failure.The results were further validated by ELISA and immunohistochemical analysis.RESULTS:We identified high expression of MMP-7 and MMP-10 and low expression of TIMP-4 in ARVC failing hearts compared to non-failing hearts by hybridization with the cytokine-specific antibody arrays containing 17 MMPs and 4 TIMPs on the chips.ELISA and immunohistochemical analyses further confirmed that differentially expressed levels of MMP-7, MMP-10, and TIMP-4 were observed not only in ARVC failing heart, but also in failing hearts due to ischemic (ICM) and dilated cardiomyopathy (DCM).CONCLUSION:Highly expressed MMP-7 and MMP-10 and lowly expressed TIMP-4 may be involved in the ventricular remodeling of heart failure derived from cardiomyopathy of different etiology.