MMP-3 (5A/6A) Polymorphism Does Not Influence Human Smooth Muscle Cell Invasion

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• 作者：Azhar Maqbool ; Ph.D.^&lowast ; ; ² ; Anita Keswani ; M.Sc.^&lowast ; ; ² ; Stacey Galloway ; B.Sc.^&lowast ; ; David J. O&rsquo ; Regan ; M.D. ; F.R.C.S.^&dagger ; ; ^&Dagger ; ; Stephen G. Ball ; Ph.D. ; F.R.C.P.^&lowast ; ; ^&dagger ; ; Neil A. Turner ; Ph.D.^&lowast ; ; ^&dagger ; ; Karen E. Porter ; Ph.D.^&lowast ; ; ^&dagger ; ; ^{k.e.porter@leeds.ac.uk}
• 关键词：polymorphism ; MMP-3 ; saphenous vein ; smooth muscle cell ; human ; invasion
• 刊名：Journal of Surgical Research
• 出版年：2012
• 期刊代码：299_00224804
• 类别：med
• 出版时间：15 June, 2012
• 卷：175
• 期：2
• 页码：343-349
• 文件大小：212 K

摘要

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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.

Material and 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.