Published online before print November 18, 2004, doi: 10.1161/01.ATV.0000151373.33830.41
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© 2005 American Heart Association, Inc.
Vascular Biology |
Matrix Metalloproteinase-9 (MMP-9), MMP-2, and Serum Elastase Activity Are Associated With Systolic Hypertension and Arterial Stiffness
From the Clinical Pharmacology Unit (Y., C.M.M., S.W., Z.D., K.M.-P., M.J.A., I.B.W.), University of Cambridge Addenbrooke’s Hospital Cambridge, United Kingdom; and the Department of Cardiology (P.P., J.R.C.) University of Wales College of Medicine, University Hospital Cardiff, United Kingdom.
Correspondence to Dr Yasmin, Clinical Pharmacology Unit, Addenbrooke’s Hospital, Box 110, Cambridge CB2 2QQ, UK. E-mail my105{at}medschl.cam.ac.uk
Background— Arterial stiffness is an independent determinant of cardiovascular risk, and arterial stiffening is the predominant abnormality in systolic hypertension. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes, including matrix metalloproteinase-9 (MMP-9) and MMP-2. We hypothesized that elastase activity would be related to arterial stiffness and tested this using isolated systolic hypertension (ISH) as a model of stiffening and separately in a large cohort of healthy individuals.
Methods and Results— A total of 116 subjects with ISH and 114 matched controls, as well as 447 individuals free from cardiovascular disease were studied. Aortic and brachial pulse wave velocity (PWV) and augmentation index were determined. Blood pressure, lipids, C-reactive protein, MMP-9, MMP-2, serum elastase activity (SEA), and tissue-specific inhibitor 2 of metalloproteinases were measured. Aortic and brachial PWV, MMP-9, MMP-2, and SEA levels were increased in ISH subjects compared with controls (P=0.001). MMP-9 levels correlated linearly and significantly with aortic (r=0.45; P=0.001) and brachial PWV (r=0.22; P=0.002), even after adjustments for confounding variables. In the younger, healthy subjects, MMP-9 and SEA were also independently associated with aortic PWV.
Conclusions— Aortic stiffness is related to MMP-9 levels and SEA, not only in ISH, but also in younger, apparently healthy individuals. This suggests that elastases including MMP-9 may be involved in the process of arterial stiffening and development of ISH.
The relationship between arterial stiffness and elastase activity was examined in isolated systolic hypertension (ISH), and separately in a large cohort of healthy individuals. Aortic stiffness is related to MMP-9, not only in ISH, but also in healthy individuals, suggesting elastases may be involved in the process of arterial stiffening and the development of ISH.
Key Words: MMP-9 • MMP-2 • elastase activity • pulse wave velocity • augmentation index • elastin
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