ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

Hsieh, Wen-Yeh; Kuan, Tang-Ching; Cheng, Kun-Shan; Liao, Yan-Chiou; Chen, Mu-Yuan; Lin, Pei-Heng; Hsu, Yuan-Chang; Huang, Chen-Yi; Hsu, Wei-Hua; Yu, Sheng-Yao; Lin, Chih-Sheng

A number of studies have indicated that the ACE-Ang II axis and ACE2-Ang1-7 axis not only regulate the metabolism of ECM proteins, but also modulate MMP expression and activity levels [8] . MMPs have been implicated in the pathogenesis of various lung diseases, including pleural effusions [25, 26] . The activity of MMPs within the pleural space may play a role in the formation of pleural effusions by altering the integrity of the mesothelial and endothelial cell layers and by increasing vascular permeability [10, 27] . Proteolysis by MMPs may be involved in the formation of pleural effusions by increasing vascular permeability, and thus by facilitating fluid influx into the pleural space [28] . Therefore, the presence and enzymatic activities of MMPs have been identified in pleural effusions [15, 25, 29] . Previous studies have shown that the expression of MMPs in the pleural space is altered in a variety of inflammatory and malignant diseases, suggesting that certain members of the MMP family may participate in the formation of pleural effusions [10, 15, 29] . Tissue damage is a characteristic manifestation of Mycobacterium tuberculosis infection. Proteolysis by macrophage-secreted proteases has been implicated in such destructive processes. In this regard, the proteolytic action of MMPs may be involved in the pathogenesis of tuberculosis, like many other diseases associated with tissue destruction. Several studies have reported that macrophages and monocytes release MMP-9 in response to tuberculosis or its cellular components [30, 31] . Studies have evaluated MMPs in tuberculous pleural effusions and found that the MMP activity in pleural fluid are higher in patients with tuberculosis compared with patients with transudative effusions [10, 32] . Our results are in agreement with the above findings, as the MMP-9 activity was highest in tuberculous effusions among the exudates we examined.