Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2893374 | Atherosclerosis | 2009 | 8 Pages |
Abstract
Matrix metalloproteinase-9 (MMP-9) is an important regulator of vascular smooth muscle cell (SMC) invasion and proliferation. The T allele of the â1562C/T MMP-9 promoter polymorphism reportedly confers increased MMP-9 promoter activity, plasma MMP-9 levels and susceptibility to vascular pathologies. The aim of this study was to determine whether the MMP-9 â1562C/T polymorphism directly influences endogenous MMP-9 expression levels in saphenous vein (SV) SMC cultured from patients with different genotypes. Genotyping of 408 patients revealed â1562C/T genotype frequencies of 73.3% CC, 25.0% CT and 1.7% TT. Using a standardized, controlled protocol we investigated the effects of phorbol ester (TPA) and a physiological stimulus (PDGFÂ +Â IL-1) on MMP-9 expression in cultured SV-SMC from 15 CC, 15 CT and 3 TT patients, and on PDGFÂ +Â IL-1-induced SV-SMC invasion (Boyden chamber with Matrigel barrier). A strong correlation between MMP-9 mRNA levels (real-time RT-PCR) and MMP-9 protein secretion (gelatin zymography) was observed. However, no significant differences were observed in MMP-9 expression levels, or in SV-SMC invasion, between cells with different â1562C/T genotypes. Moreover, MMP-9 promoter activity of the C and T variants was similar. Our data challenge the functional nature of the â1562C/T polymorphism and its capacity to modulate MMP-9 expression levels and SV-SMC invasion, and hence susceptibility to vascular pathologies in vivo.
Related Topics
Health Sciences
Medicine and Dentistry
Cardiology and Cardiovascular Medicine
Authors
Azhar Maqbool, Neil A. Turner, Stacey Galloway, Kirsten Riches, David J. O'Regan, Karen E. Porter,