Title
Matrix metalloproteinases in premature coronary atherosclerosis: Influence of inhibitors, inflammation, and genetic polymorphisms
Author
Nanni, S.
Melandri, G.
Hanemaaijer, R.
Cervi, V.
Tomasi, L.
Altimari, A.
van Lent, N.
Tricoci, P.
Bacchi, L.
Branzi, A.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly in the occurrence of acute coronary syndrome (ACS). Little is known about human in vivo MMP regulation in CAD. The expression and regulation of MMPs and their tissue inhibitors (TIMPs) were evaluated in premature CAD. The distribution of MMP-3 5A/6A and MMP-9 C/T promoter polymorphisms and MMP-9 A/G exon-6 polymorphism were investigated in 200 consecutive male premature CAD patients (aged ≤55 years) and 201 age-matched male blood donors. Plasma concentrations/activities of MMP-2 and MMP-9 were also measured, as were plasma concentrations of MMP-3, TIMP-1, and TIMP-2 in 80 patients (49 with ACSs and 31 with stable CAD) and 40 controls. Inflammation markers were also obtained. MMP genetic polymorphism distributions did not vary between patients and controls and did not seem to influence their respective MMP plasma levels. Patients showed increased MMP-9 and TIMP-1 concentrations and decreased TIMP-2 concentration and MMP-2 total activity (all P ≤ 0.002). Overall, TIMP-1 correlated with C-reactive protein (CPR) (r = 0.594, P < 0.001) and haptoglobin (r = 0.276, P = 0.005), whereas MMP-2 activity correlated inversely with haptoglobin (r = -0.195, P = 0.032). Blood glucose correlated positively with TIMP-1 concentration (r = 0.711, P < 0.001) and negatively with MMP-2 activity (r = -0.250, P = 0.006). In conclusion, MMP and TIMP plasma levels in premature CAD are linked to clinical presentation and markers of inflammation and metabolic disorders rather than to genetic polymorphisms. © 2007 Mosby, Inc. All rights reserved.
Subject
Health
Biomedical Research
biological marker
gelatinase A
gelatinase B
glucose
haptoglobin
matrix metalloproteinase
stromelysin
tissue inhibitor of metalloproteinase
tissue inhibitor of metalloproteinase 1
tissue inhibitor of metalloproteinase 2
adult
article
controlled study
coronary artery atherosclerosis
correlation analysis
enzyme activity
enzyme blood level
exon
genetic polymorphism
glucose blood level
human
human tissue
inflammation
major clinical study
male
metabolic disorder
pathogenesis
priority journal
protein expression
protein localization
To reference this document use:
http://resolver.tudelft.nl/uuid:1ae8a3d8-d71b-4718-99ea-129f249c6129
DOI
https://doi.org/10.1016/j.trsl.2006.09.001
TNO identifier
239895
ISSN
1931-5244
Source
Translational Research, 149 (3), 137-144
Document type
article