Int J Biol Sci 2012; 8(8):1197-1205. doi:10.7150/ijbs.5087 This issue

Research Paper

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

Wen-Yeh Hsieh1,2,3,*, Tang-Ching Kuan1,*, Kun-Shan Cheng1,4, Yan-Chiou Liao1, Mu-Yuan Chen1, Pei-Heng Lin1, Yuan-Chang Hsu1, Chen-Yi Huang2, Wei-Hua Hsu2, Sheng-Yao Yu2, Chih-Sheng Lin1✉

1. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan;
2. Division of Chest Medicine, Department of Internal Medicine, Mackay Memorial Hospital, Hsinchu, Taiwan;
3. Medical Department, Mackay Medical College, Taipei, Taiwan;
4. Division of Cardiology, Department of Pediatrics, Mackay Memorial Hospital, Hsinchu, Taiwan.
* Equal contribution as the first author.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Hsieh WY, Kuan TC, Cheng KS, Liao YC, Chen MY, Lin PH, Hsu YC, Huang CY, Hsu WH, Yu SY, Lin CS. ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions. Int J Biol Sci 2012; 8(8):1197-1205. doi:10.7150/ijbs.5087. Available from

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Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates.

Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28).

Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions.

Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.

Keywords: angiotensin converting enzyme, angiotensin converting enzyme 2, exudative effusion, matrix metalloproteinase-9, tuberculous effusion.