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

It is interesting that significantly increased ACE activity combined with markedly decreased ACE2 activity was measured in tuberculous effusions. This result confirms that abnormal RAS metabolism in pleural spaces may be related to tuberculous pleurisy. It was reported that overexpression of ACE2 may inhibit MMP-9 activity [19] , and ACE2 deficiency leads to increased MMP-9 levels [20] . In inflammatory signalling pathways study, Ang II could stimulate human monocytic U-937 cells to increase MMP-9 expression and activity significantly via activated NF-κB, JNK, and p38 [21] . The ACE inhibitor, captopril, was administrated to isoprenaline-induced left ventricular fibrosis rats and showed that captopril significantly enhanced the isoprenaline-induced myocardial fibrosis and augmented the isoprenaline-induced MMP-9 expression [22] . In addition, ACE2 and Ang 1-7, the regulators in RAS opposed Ang II effect, could affect MMP-9 expression. Overexpression of ACE2 reduces the invasive ability in vitro according to the down-regulation of MMP-2 and MMP-9 [23] . Ang 1-7 revealed the anti-migration and anti-invasion effect mediated through inactivation of the PI3K/Akt, P38 and JNK signal pathways to reduce the expression and activity of MMP-2 and MMP-9 [24] . According to our results, we conclude that reduction in ACE2 along with induction of MMP-9 activity occurred. Our observations of decreased ACE2 and increased MMP-9 activity in tuberculous effusions confirm this conclusion.