title: The Effects of Angiotensin Converting Enzyme Inhibitors (ACE-I) on Human N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) Levels: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues.
  
  
  OBJECTIVE
  To systematically review the effects of ACE-Is on Ac-SDKP levels in human tissues.
  
  
  METHODS
  We searched five electronic databases (1996 to 2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO.
  
  
  RESULTS
  Four studies with a total of 206 participants met the inclusion criteria. Three studies (106 participants) assessed the change in plasma levels of Ac-SDKP following ACE-I administration in healthy humans. The administration of an ACE-I was associated with an increase in Ac-SDKP levels (mean difference (MD) 5.07 pmol/ml (95% confidence intervals (CI) 0.64 pmol/ml to 9.51 pmol/ml)). Two studies with 100 participants further assessed the change in Ac-SDKP level in humans with renal failure using ACE-I. The administration of an ACE-I was associated with a significant increase in Ac-SDKP levels (MD 8.94 pmol/ml; 95% CI 2.55 to 15.33; I2 = 44%).
  
  
  CONCLUSIONS
  ACE-I increased Ac-SDKP levels in human plasma. These findings provide the rationale for testing the impact of ACE-I on Ac-SDKP levels and fibrosis in tuberculous pericarditis.
authors.affiliation: Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Ayanda Trevor
authors.initials: AT
authors.lastname: Mnguni
authors.affiliation: Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Engel
authors.affiliation: Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Borkum
authors.affiliation: Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005355:Fibrosis; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018579:Patient Selection; D010495:Pericarditis, Tuberculous / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; C058504:goralatide