Document Detail

Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease.
MedLine Citation:
PMID:  16054454     Owner:  NLM     Status:  MEDLINE    
Endogenous matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are important mediators of extracellular matrix remodeling, which is integral to plaque progression in coronary artery disease. In addition, high levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. We hypothesized that circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were abnormal in patients who had stable coronary artery disease, and these levels were compared with those in matched controls. We also hypothesized correlations of MMPs, TIMPs, and sCD40L to each other and to high-sensitivity C-reactive protein (a proinflammatory marker), white blood cell count, severity of coronary artery disease (based on angiographic measurements of atherosclerotic burden), and coronary collateralization. We studied 204 adult patients who attended our unit for outpatient diagnostic cardiac catheterization for the investigation of suspected coronary artery disease. Coronary angiograms were scored for atheroma burden and stenosis by 2 independent observers. Circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were measured by enzyme-linked immunosorbent assay. Plasma levels of MMP-9 (p = 0.0099), TIMP-2 (p = 0.0019), and sCD40L (p <0.001), but not TIMP-1 (p = 0.463) were high in patients compared with healthy controls. In patients who had coronary artery disease, MMP-9 and high-sensitivity C-reactive protein levels were significantly higher in women than in men. Only MMP-9 correlated modestly with total white blood cell count (Spearman's correlation, r = 0.274, p = 0.002). Logistic regression of cardiovascular risk factors showed that only white blood cell count was independently associated with MMP-9 (p = 0.02). After standardizing for atheroma and stenosis scores, there were no statistically significant differences in our research indexes in patients who had angiographic collaterals compared with those who did not. In conclusion, stable coronary artery disease is associated with abnormal circulating levels of MMP-9, TIMP-2, and sCD40L, which do not appear to related to each other or to severity of coronary artery disease or collateralization. The gender difference in high-sensitivity C-reactive protein and MMP-9 levels may provide insight into the pathophysiology of coronary artery disease in men and women, and further studies are warranted to explore this potential link.
Muzahir H Tayebjee; Gregory Y H Lip; Kiat T Tan; Jeetesh V Patel; Elizabeth A Hughes; Robert J MacFadyen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of cardiology     Volume:  96     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-01     Completed Date:  2005-09-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  339-45     Citation Subset:  AIM; IM    
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
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MeSH Terms
Biological Markers / blood
C-Reactive Protein / metabolism
CD40 Ligand / blood*
Case-Control Studies
Coronary Angiography
Coronary Artery Disease / blood*,  radiography
Disease Progression
Enzyme-Linked Immunosorbent Assay
Logistic Models
Matrix Metalloproteinase 9 / blood*
Middle Aged
Sensitivity and Specificity
Severity of Illness Index
Statistics, Nonparametric
Tissue Inhibitor of Metalloproteinase-1 / blood
Tissue Inhibitor of Metalloproteinase-2 / blood*
Reg. No./Substance:
0/Biological Markers; 0/Tissue Inhibitor of Metalloproteinase-1; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 147205-72-9/CD40 Ligand; 9007-41-4/C-Reactive Protein; EC Metalloproteinase 9

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