title: ACE/ACE2 ratio and MMP-9 activity as potential biomarkers in tuberculous pleural effusions.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Wen-Yeh
authors.initials: WY
authors.lastname: Hsieh
authors.forename: Tang-Ching
authors.initials: TC
authors.lastname: Kuan
authors.forename: Kun-Shan
authors.initials: KS
authors.lastname: Cheng
authors.forename: Yan-Chiou
authors.initials: YC
authors.lastname: Liao
authors.forename: Mu-Yuan
authors.initials: MY
authors.lastname: Chen
authors.forename: Pei-Heng
authors.initials: PH
authors.lastname: Lin
authors.forename: Yuan-Chang
authors.initials: YC
authors.lastname: Hsu
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Huang
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Hsu
authors.forename: Sheng-Yao
authors.initials: SY
authors.lastname: Yu
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Lin
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010996:Pleural Effusion / Q000209:etiology / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D018709:Statistics, Nonparametric; D014396:Tuberculosis, Pleural / Q000150:complications / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D020780:Matrix Metalloproteinase 9
keywords: angiotensin converting enzyme; angiotensin converting enzyme 2; exudative effusion; matrix metalloproteinase-9; tuberculous effusion.