title: Increased levels of leukocyte-derived MMP-9 in patients with stable angina pectoris.
abstract: OBJECTIVE
  There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA).
  
  
  METHODS
  In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR.
  
  
  RESULTS
  Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p<0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p<0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p<0.01.
  
  
  CONCLUSIONS
  Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that the leukocytes are more prone to release and produce MMP-9 in symptomatic and angiographically verified CAD-a phenomenon that may have clinical implications in the course of disease.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Jönsson
authors.forename: Anna
authors.initials: A
authors.lastname: Lundberg
authors.forename: Hanna
authors.initials: H
authors.lastname: Kälvegren
authors.forename: Ida
authors.initials: I
authors.lastname: Bergström
authors.forename: Aleksander
authors.initials: A
authors.lastname: Szymanowski
authors.forename: Lena
authors.initials: L
authors.lastname: Jonasson
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000097:blood*; D000792:Angiography / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D009195:Peroxidase; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9