Abstract
The extracellular matrix is vital for maintaining tissue integrity, and the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system is involved in the regulation of extracellular matrix metabolism. Extracellular matrix turnover plays an important role in the change of large arterial mechanical properties in hypertension. However, the association of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) system and arterial stiffness is not straightforward and existing data are rather limited. Our objective is to explore the impact of the MMP-9/TIMP-1 system on large arterial stiffness in patients with essential hypertension. An automatic pulse wave velocity (PWV) measuring system was used to examine carotid-femoral PWV (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central elastic large arterial and peripheral muscular medium-sized arterial elasticity, respectively; and serum MMP-9 and TIMP-1 levels, along with a number of other established biomarkers, were measured by enzyme-linked immunosorbent assay (ELISA) in 202 essential hypertensive patients and 54 age and gender-matched control subjects. Compared with the control subjects, hypertensive patients exhibited higher levels of MMP-9 (p=0.001) and TIMP-1 (p=0.002). Spearman's correlation analysis showed that serum levels of MMP-9 (p=0.014) and TIMP-1 (p=0.005) were significantly and positively correlated with CFPWV in hypertensive patients. A stepwise multiple regressive analysis demonstrated that age, systolic blood pressure, heart rate and TIMP-1 were independent predictors of CFPWV in patients with essential hypertension (adjusted r2=0.458). In conclusion, our results imply that the MMP-9/TIMP-1 system may play an important role in the determination of arterial function, and these findings may have implications for the involvement of MMP-9/TIMP-1 system in the pathophysiology of cardiovascular disease.
Similar content being viewed by others
Article PDF
References
Grundy SM : Inflammation, hypertension, and the metabolic syndrome. JAMA 2003; 290: 3000–3002.
Amar J, Ruidavets JB, Chamontin B, Drouet L, Ferrieres J : Arterial stiffness and cardiovascular risk factors in a population-based study. J Hypertens 2001; 19: 381–387.
Laurent S, Boutouyrie P, Asmar R, et al: Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236–1241.
Asmar R, Rudnichi A, Blacher J, London GM, Safar ME : Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations. Am J Hypertens 2001; 14: 91–97.
Asmar R, Benetos A, Topouchian J, et al: Assessment of arterial distensibility by automatic pulse wave velocity measurement: validation and clinical application studies. Hypertension 1995; 26: 485–490.
Ni Y, Wang H, Hu D, Zhang W : The relationship between pulse wave velocity and pulse pressure in Chinese patients with essential hypertension. Hypertens Res 2003; 26: 871–874.
Bland JM, Altman DG : Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: 307–310.
Visse R, Nagase H : Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92: 827–839.
Rodriguez-Pla A, Bosch-Gil JA, Rossello-Urgell J, Huguet-Redecilla P, Stone JH, Vilardell-Tarres M : Metalloproteinase-2 and -9 in giant cell arteritis: involvement in vascular remodeling. Circulation 2005; 112: 264–269.
Yasmin, McEniery CM, Wallace S, et al: Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness. Arterioscler Thromb Vasc Biol 2005; 25: 372–378.
Karakaya O, Barutcu I, Esen AM, et al: Relationship between circulating plasma matrix metalloproteinase-9 (gelatinase-B) concentration and aortic root dilatation. Am J Hypertens 2006; 19: 361–365.
Jacob MP : Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother 2003; 57: 195–202.
Tayebjee MH, Nadar SK, Macfadyen RJ, Lip GY : Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension. Relationship to tissue Doppler indices of diastolic relaxation. Am J Hypertens 2004; 17: 770–774.
Lindsay MM, Maxwell P, Dunn FG : TIMP-1: a marker of left ventricular diastolic dysfunction and fibrosis in hypertension. Hypertension 2002; 40: 136–141.
Bouvet C, Gilbert LA, Girardot D, deBlois D, Moreau P : Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition. Hypertension 2005; 45: 432–437.
Boutouyrie P, Laurent S, Benetos A, Girerd XJ, Hoeks AP, Safar ME : Opposing effects of aging on distal and proximal large arteries in hypertensives. J Hypertens Suppl 1992; 10: S87–S89.
Fichtlscherer S, Heeschen C, Zeiher AM : Inflammatory markers and coronary artery disease. Curr Opin Pharmacol 2004; 4: 124–131.
Chua CC, Hamdy RC, Chua BH : Angiotensin II induces TIMP-1 production in rat heart endothelial cells. Biochim Biophys Acta 1996; 1311: 175–180.
Ishikawa J, Kario K, Matsui Y, et al: Collagen metabolism in extracellular matrix may be involved in arterial stiffness in older hypertensive patients with left ventricular hypertrophy. Hypertens Res 2005; 28: 995–1001.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tan, J., Hua, Q., Xing, X. et al. Impact of the Metalloproteinase-9/Tissue Inhibitor of Metalloproteinase-1 System on Large Arterial Stiffness in Patients with Essential Hypertension. Hypertens Res 30, 959–963 (2007). https://doi.org/10.1291/hypres.30.959
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.30.959
Keywords
This article is cited by
-
Does body mass index or waist-hip ratio correlate with arterial stiffness based on brachial-ankle pulse wave velocity in Chinese rural adults with hypertension?
BMC Cardiovascular Disorders (2021)
-
Rice bran protein hydrolysates reduce arterial stiffening, vascular remodeling and oxidative stress in rats fed a high-carbohydrate and high-fat diet
European Journal of Nutrition (2018)
-
Role of Thioredoxin in Age-Related Hypertension
Current Hypertension Reports (2018)
-
Low serum adiponectin level is associated with metabolic syndrome and is an independent marker of peripheral arterial stiffness in hypertensive patients
Diabetology & Metabolic Syndrome (2017)
-
Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
Cardiovascular Diabetology (2017)