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.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.

Circulating Matrix Metalloproteinase-2 and -9 Enzyme Activities in the Children with Ventricular Septal Defect

“…The activities of MMP-2 and MMP-9 in the plasma were measured by gelatin gel zymography as previously described 19, 20. The plasma was mixed with 2x zymography sample buffer (0.125 M Tris-HCl, pH 6.8, 20% [v/v] glycerol, 4% [w/v] SDS, and 0.005% bromophenol blue), incubated for 10 min, and then loaded into SDS-PAGE that was performed in 7% acrylamide gels containing 0.1% (w/v) gelatin (Sigma-Aldrich, St. Louis, MO, USA).…”

Tissue Inhibitor of Metalloproteinase-1 Is Responsible for Residual Pleural Thickening in Pleural Tuberculosis

“…For example, collagenases (MMP-1, MMP-8 and MMP-13) degrade type I collagen, whereas gelatinases (MMP-2 and MMP-9) degrade gelatin (denatured collagen) and type IV collagen, a major component of basement membranes. In humans, MMPs levels were higher in exudates compared to transudates and additionally increased in pleural tuberculosis compared to non-tuberculosis effusion (Eickelberg et al 1997;Hoheisel et al 2001;Vatansever et al 2009;Hsieh et al 2012). Furthermore, MMP-9 may be key in tissue remodeling and scaring that lead to long-term fibrosis (Woessner 1991;Kotyza et al 2004).…”

Association between Serum Angiotensin-converting Enzyme 2 Level with Postoperative Morbidity and Mortality after Major Pulmonary Resection in Non-small Cell Lung Cancer Patients

“…ACE2 protein also appears to be the entry-point receptor for the severe acute respiratory syndrome (SARS) coronavirus [18,19]. In addition, interplay between ACE and ACE2 reportedly plays a pivotal role in the development of tuberculous pleural effusions [20]. Thus, ACE2 appears directly involved in pulmonary vascular regulation as well as in pulmonary infection and pleural effusion.…”

“…In addition, our findings also suggest that supplementing ACE2 could be a potential therapy for preventing or improving postoperative morbidities after major pulmonary resection. Given the important role of Ang II/ACE2 signalling in pulmonary vascular regulation, pulmonary infection and pleural effusion, and possibly atrial fibrillation [15][16][17][18][19][20][21], an increase of ACE2 after major pulmonary resection, albeit short-lived, may be a critical compensatory mechanism against initiation of early postoperative morbidities, which leads to reduced manifestation of postoperative morbidities and mortality. Further studies are needed to uncover the underlying mechanisms.…”