High Blood Press Cardiovasc Prev 2006; 13 (2): 47-52 ORIGINAL RESEARCH ARTICLE 1120-9879/06/0002-0047/$39.95/0 © 2006 Adis Data Information BV. All rights reserved. Matrix Metalloproteinase-2, -9 and Tissue Inhibitor Metalloproteinase-1 in Patients with Hypertension Before and After Doxazosin Therapy Giuseppe Derosa, 1 Arrigo F.G. Cicero, 2 Angela D’Angelo, 1 Carmine Tinelli, 3 Leonardina Ciccarelli, 1 Mario N. Piccinni, 1 Fabio Pricolo, 1 Sibilla Salvadeo, 1 Lorenza Montagna, 1 Elena Fogari, 1 Alessia Gravina, 1 Ilaria Ferrari, 1 Simona Galli, 1 Sonia Paniga 1 and Roberto Fogari 1 1 Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy 2 ‘D. Campanacci’ Department of Clinical Medicine and Applied Biotechnology, ‘G. Descovich’ Atherosclerosis Study Center, University of Bologna, Bologna, Italy 3 Biometric Unit, IRCCS Policlinico S. Matteo, Pavia, Italy Background: There are conflicting data in the literature regarding both the expression pattern of the vascular Abstract metalloproteinase (MMP) system and its tissue inhibitors (TIMPs) in human hypertension and the effect of antihypertensive drugs in modifying the MMP/TIMP system. This study was designed to test the hypothesis that MMP-2, MMP-9 and TIMP-1 are altered in hypertension reflecting alterations in extracellular matrix turnover. Moreover, the aim of the study was to assess whether chronic antihypertensive treatment with doxazosin would normalise these alterations. Materials and results: We measured plasma levels and activities of MMP-2, MMP-9 and TIMP-1 in 44 hypertensive patients before and after 4 months of doxazosin treatment. MMP-2 levels and activity were significantly lower in the hypertensive group after treatment (p < 0.0001) compared with respective values before treatment. Significant decrease was also observed for MMP-9 level and activity (p < 0.0001) and for TIMP-1 (p < 0.0001) in hypertensive patients after antihypertensive treatment. Conclusions: Plasma levels and activities of MMP-2, MMP-9 and TIMP-1 are decreased in hypertensive patients after treatment compared with respective values before treatment. This may demonstrate that antihypertensive drugs modify the MMP/TIMP system, contributing to the mechanisms of vascular remodelling. Background tion of ECM components, particularly collagen, as well as altera- tions in ECM architecture or cell-ECM attachments. [3] The matrix metalloproteinase (MMP) proteolytic system and its Recently, Zervoudaki et al. [4,5] showed that plasma levels of natural tissue endogenous inhibitors (TIMPs) are involved in the active MMP-2 and MMP-9 are depressed in patients with essential regulation of extracellular matrix (ECM) metabolism. Changes in hypertension, which may reflect abnormal ECM metabolism. Pre- MMPs or TIMP activity may contribute to vascular remodelling in vious studies showed diminished MMPs activity in hypertensive hypertensive patients by modulating ECM profiles and interacting patients. [6] Indeed, Laviades et al. [7] reported lower levels of with adhesion receptors. [1] Indeed, MMPs may participate in rup- MMP-1 and higher levels of TIMP-1 in patients with essential ture of the atherosclerotic plaque. [2] hypertension than in controls, suggesting that systemic extracellu- Hypertension is usually associated with the development of lar degradation of collagen type 1 is depressed in hypertension. On vascular fibrosis. This pathological process is characterised by the contrary, significant increases in circulating MMP-9 and structural changes in the arterial wall caused by increased deposi-