Metalloproteases/anti-metalloproteases imbalance in chronic obstructive pulmonary disease: genetic factors and treatment implications
Metalloproteases/anti-metalloproteases imbalance in chronic obstructive pulmonary disease: genetic factors and treatment implications
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DOI：
10.1097/01.mcp.0000410743.98087.12
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发表时间：
2011-12-01
影响因子：
3.3
通讯作者：
Costarelli, Laura
中科院分区：
文献类型：
--
作者：
Mocchegiani, Eugenio;Giacconi, Robertina;Costarelli, Laura
综述的目的是描述基质金属蛋白酶（MMP）、A去整合素和金属蛋白酶（ADAM）、MMP组织抑制剂（TIMP）多态性的参与以及α 2巨球蛋白的作用。（α-2 M）在慢性阻塞性肺疾病（COPD）发展和进展中的作用，重点是单独使用合成MMP抑制剂或与COPD治疗中使用的当前药物联合使用以恢复MMP/TIMPs失衡。最新发现COPD是老年人死亡的主要原因之一。其特征在于气流限制的进行性发展，表现为一秒用力呼气量（FEV 1）降低和FEV 1/用力肺活量百分比降低。主要的致病作用是由金属蛋白酶（MMP，亚当斯）/抗金属蛋白酶（TIMP，α-2M）失衡发挥的，这是MMP过度产生而不能被TIMP或α-2M充分抵消的原因。因此，肺细胞外基质被破坏，阻塞小气道和外观的肺气肿.SummaryThe疾病主要是由于暴露于香烟烟雾或有毒气体和空气污染物，但也涉及遗传因素。其中MMPs（MMP 1、MMP 2、MMP 9、MMP 12）、亚当斯（ADAM 33）和TIMPs（TIMP 1、TIMP 2）基因多态性与肺癌的发生密切相关，其中炎症和吸烟习惯起着关键作用，尤其是在不良等位基因携带者中。这些多态性与当前药物之间的关联为个性化治疗铺平了道路，在临床水平上具有很大的影响。
Purpose of reviewThe aim is to describe the involvement of matrix metalloprotease (MMP), A Disintegrin And Metalloproteases (ADAM), tissue inhibitors of MMP (TIMP) polymorphisms and the role of alpha-2 Macroglobulin (alpha-2M) in chronic obstructive pulmonary disease (COPD) development and progression, with a focus on interventions with synthetic MMP inhibitors alone or associated with current drugs used in COPD therapy in order to restore MMPs/TIMPs imbalance.Recent findingsCOPD is one of the major causes of death in the elderly. It is characterized by progressive development of airflow limitation manifested by decreased forced expiratory volume in one second (FEV1) and reduction in the percentage of FEV1/forced vital capacity. The major pathogenic role is played by metalloproteases (MMPs, ADAMs)/anti-metalloproteases (TIMPs, alpha-2M) imbalance, which is responsible for MMP overproduction not sufficiently counteracted by TIMPs or alpha-2M. As a consequence, the lung extracellular matrix is destroyed with obstruction of small airways and appearance of emphysema.SummaryThe disease is mainly caused by exposure to cigarette smoke or noxious gases and air pollutants, but also genetic factors are involved. Among them, polymorphisms of MMPs (MMP1, MMP2, MMP9, MMP12), ADAMs (ADAM33) and TIMPs (TIMP1, TIMP2) are relevant, in which the inflammation and the smoking habit play key roles especially in unfavorable allele carriers. The association between these polymorphisms and the current drugs paves the way for personalized therapy with a great impact at clinical level.