Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema
Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema
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DOI：
10.1371/journal.pone.0056352
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发表时间：
2013-02-18
期刊：
影响因子：
3.7
通讯作者：
Foronjy, Robert F.
中科院分区：
文献类型：
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作者：
D'Armiento, Jeanine M.;Goldklang, Monica P.;Foronjy, Robert F.
理由：虽然基质金属蛋白酶 (MMP) 在 COPD 的发病机制中至关重要，但它们作为疾病生物标志物的效用仍不确定。本研究旨在确定支气管肺泡灌洗 (BALF) 或血浆 MMP 测量是否与肺气肿的疾病严重程度或功能下降相关。方法：酶联免疫吸附测定和 luminex 测定测量非吸烟者、肺功能正常的吸烟者和中重度肺气肿受试者的 BALF 和血浆中的 MMP-1、-9、-12 和基质金属蛋白酶-1 组织抑制剂。在 101 名肺气肿受试者队列中进行相关分析，以确定 MMP 或 TIMP-1 水平是否与关键疾病参数或 18 个月内肺功能的变化相关。 主要结果：与非吸烟对照相比，肺气肿队列中 MMP 和 TIMP-1 BALF 水平显着升高。尽管MMP-1在正常吸烟者和肺气肿组中均升高，但胶原酶活性仅在肺气肿组中升高。与 BALF 相比，与对照组相比，肺气肿组的血浆 MMP-9 和 TIMP-1 水平实际上有所降低。在肺气肿受试者的 BALF 和血浆中，MMP 和 TIMP-1 测量值与重要的疾病参数没有相关性，并且不能预测随后的功能衰退。结论：肺气肿的 BALF 和血浆中的 MMP 发生改变；然而，MMP 的变化与疾病强度或进展参数的相关性较差。尽管 MMP 在 COPD 的发病机制中至关重要，但这些研究结果表明，测量 MMP 作为该疾病的预后标志物的效用有限。
Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema.Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period.Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline.Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease.