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. CONCLUSION: 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.
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. CONCLUSION: 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.
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