title: The effect of prolonged systemic doxycycline therapy on serum tissue degrading proteinases in coronary bypass patients: a randomized, double-masked, placebo-controlled clinical trial.
abstract: OBJECTIVE
  Serum matrix metalloproteinases (MMP-8, MMP-7) and their regulators may be associated with the risk of incident cardiovascular disease events. Doxycycline can be used as matrix metalloproteinase (MMP) inhibitor independent of its antimicrobial activity. We aimed to investigate serum inflammatory biomarkers during 4 months of doxycycline therapy in coronary bypass patients.
  
  
  METHODS
  Thirty-one non-smoking men who had previous coronary bypass surgery were randomly assigned to receive placebo or 100 mg doxycycline daily for 4 months. Serum samples were collected at baseline before the treatment, and at 2, 4, and 10 months. Serum levels of MMP-7, tissue inhibitor of matrix metalloproteinase (TIMP)-1, myeloperoxidase, and neutrophil elastase were analyzed with enzyme-linked immunosorbent assay, MMP-8 by immunofluorometric assay, and C-reactive protein by rate nephelometry.
  
  
  RESULTS
  At baseline, no significant differences existed between the two groups. Serum levels of MMP-8, MMP-7, and MMP-8/TIMP-1 were and remained lower (p = 0.034, p = 0.041, and NS) in the doxycycline group relative to the placebo group at 4 months of follow-up.
  
  
  CONCLUSIONS
  Doxycycline decreases the systemic inflammatory burden in patients with myocardial infarction and especially down-regulates MMP-7, MMP-8, and MMP-8/TIMP-1. Doxycycline might prevent or reduce the risk of secondary myocardial infarctions by providing a systemic anti-proteolytic and -inflammatory shield.
authors.affiliation: Oral and Maxillofacial Department, Oulu University Hospital, Oulu, Finland.
authors.forename: Immi
authors.initials: I
authors.lastname: Kormi
authors.forename: Hatem
authors.initials: H
authors.lastname: Alfakry
authors.forename: Taina
authors.initials: T
authors.lastname: Tervahartiala
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D002097:C-Reactive Protein; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D004318:Doxycycline