title: Transcription activity of MMP-2 and MMP-9 metalloproteinase genes and their tissue inhibitor (TIMP-2) in acute coronary syndrome patients.
abstract: BACKGROUND
  Acute coronary syndromes (ACS) are a consequence of coronary vessel atherosclerosis and they are a leading cause of death in industrialized countries. One of the ACS causative factors is the deranged ratio equilibrium of the matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMPs/TIMPs).
  
  
  OBJECTIVE
  Assessment of transcriptional activity of metalloproteinase genes using Human Genome-U133A oligonucleotide microarrays and selection of candidate genes differentiating ACS patients from healthy subjects and finally, QRT-PCR (quantitative real time polymerase chain reaction) confirmation of the results.
  
  
  METHODS
  The study involved 67 ACS patients, admitted on a consecutive basis, to the Cardiology Clinic as well as 24 healthy subjects (control).
  
  
  METHODS
  Ribonucleic acid isolated from peripheral blood mononuclear cells was analyzed by QRT-PCR. Transcriptional activity of the analyzed gene was assessed with TaqMan gene expression assays.
  
  
  METHODS
  U Mann-Whitney test was used to compare the results.
  
  
  RESULTS
  Homogeneity of the investigated group was assessed through hierarchical clusterization whereas the nine genes differentiating ACS patients from healthy persons were selected using the Bland-Altman technique. Among these genes three (platelet derived growth factor D, NUAK family SNF1-like kinase 1 and peroxisomal biogenesis factor 1) showed decreased transcriptional activity whereas the remaining six genes (MMP-2 and MMP-9, CDK5RAP3, transmembrane BAX inhibitor motif containing 1, adenylate cyclase-associated protein 1 and TIMP-2) were increased. MMP-2, MMP-9 and TIMP-2 were further characterized by QRT-PCR.
  
  
  CONCLUSIONS
  The obtained results permit to conclude that the increased expression of MMP-2 and MMP-9 metalloproteinases and their tissue inhibitor (TIMP-2) is responsible for disturbed equilibrium of the metalloproteinase/tissue inhibitors system and as a consequence, for destabilization of atherosclerotic plaque and occurrence of the acute coronary syndrome in the investigated group of patients.
authors.affiliation: Department of Epidemiology, Medical University of Silesia, Katowice, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Dabek
authors.forename: J
authors.initials: J
authors.lastname: Glogowska-Ligus
authors.forename: B
authors.initials: B
authors.lastname: Szadorska
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000235:genetics; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D019914:Taq Polymerase; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019914:Taq Polymerase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9