Serum tissue inhibitors of metalloproteinases 1 (TIMP-1) and carotid atherosclerosis and aortic arterial stiffness.
BACKGROUND
The results of experimental studies have suggested that matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in vascular remodeling. In a population-based study, we report the relationships of serum TIMP-1 with carotid intima-media thickness, carotid plaques and aortic arterial stiffness.


METHODS
Free health examinations were performed on 238 men free of coronary heart diseases (aged 56.5 +/- 10.4 years, 57.1% were hypertensive). Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA) and assessment of atherosclerotic plaques in the extracranial carotid arteries.


RESULTS
The percentage of subjects with plaques was lower in subjects with low TIMP-1 values (P for trend = 0.0001). In multivariate analysis adjusted for age, body mass index, smoking habits, total cholesterol, triglycerides, C-reactive protein, heart rate, diabetes and systolic blood pressure, the odds ratio of carotid plaques in subjects with high values of TIMP-1 (tertile 3) compared to those with low values (tertile 1) was 2.89 (95% confidence interval 1.12-7.47, P < 0.01). TIMP-1 was positively associated with CCA-IMT and PWV in univariate analysis. However, the associations disappeared once age and systolic blood pressure were taken into account in the multivariate analysis.


CONCLUSIONS
This study shows that there is a differential association of TIMP-1 with PWV, CCA-IMT and carotid plaques. Our results suggest that TIMP-1 might be involved in plaque formation.
Zureik
Mahmoud
M
National Institute of Health and Medical Research (INSERM), Unit 508, Lille, France. mahmoud.zureik@pasteur-lille.fr
Beaudeux
Jean-Louis
JL
Courbon
Dominique
D
Bénétos
Athanase
A
Ducimetière
Pierre
P
D000368:Aged; D001011:Aorta / Q000503:physiopathology; D001783:Blood Flow Velocity; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000097:blood* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014463:Ultrasonography; D014655:Vascular Resistance / Q000502:physiology
D019715:Tissue Inhibitor of Metalloproteinase-1