title: MMP-3 (5A/6A) polymorphism does not influence human smooth muscle cell invasion.
abstract: BACKGROUND
  Stromelysin (MMP-3) is an important regulator of vascular smooth muscle cell (SMC) invasion, a key contributor to saphenous vein (SV) bypass graft failure. The 5A allele of the common -1612 MMP-3 5A/6A promoter polymorphism reportedly confers increased promoter activity, MMP-3 tissue expression, and susceptibility to a number of vascular pathologies. The aim of this study was to determine whether the MMP-3 5A/6A polymorphism directly influences endogenous MMP-3 expression levels and, consequently, cell invasion, in SV-derived SMC cultured from patients with different genotypes.
  
  
  METHODS
  Genotyping of 226 patients revealed -1612 MMP-3 5A/6A genotype frequencies of 20.8% 5A/5A, 52.7% 5A/6A, and 26.5% 6A/6A. Using a standardized, controlled protocol, we investigated cytokine- and growth factor-induced MMP-3 expression (real-time polymerase chain reaction [RT-PCR], ELISA) and SV-SMC invasion (Boyden chamber with Matrigel barrier) using cultured SV-SMC from patients with different MMP-3 genotypes.
  
  
  RESULTS
  Despite observing a strong correlation between MMP-3 mRNA levels and MMP-3 protein secretion, no significant differences were apparent in MMP-3 expression levels or cell invasion between cells with different MMP-3 5A/6A genotypes.
  
  
  CONCLUSIONS
  Our data suggest that the MMP-3 5A/6A promoter polymorphism in isolation does not influence levels of MMP-3 secretion or cellular invasion in human SV-SMC.
authors: Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds, UK.
authors: Azhar
authors: A
authors: Maqbool
authors: Anita
authors: A
authors: Keswani
authors: Stacey
authors: S
authors: Galloway
authors: David J
authors: DJ
authors: O'Regan
authors: Stephen G
authors: SG
authors: Ball
authors: Neil A
authors: NA
authors: Turner
authors: Karen E
authors: KE
authors: Porter