Matrix Metalloproteinase-2, -9 and Tissue Inhibitor Metalloproteinase-1 in Patients with Hypertension Before and After Doxazosin Therapy.

Background: There are conflicting data in the literature regarding both the expression pattern of the vascular 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