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Type: Artigo de periódico
Title: Comprehensive Evaluation of the Effects of Enalapril on Matrix Metalloproteinases Levels in Hypertension
Author: Fontana, Vanessa
Silva, Pamela S.
Izidoro-Toledo, Tatiane C.
Biagi, Celso
Oliveira, Eduardo B.
Gerlach, Raquel F.
Tanus-Santos, Jose E.
Abstract: Angiotensin-converting enzyme inhibitors (ACEi) may downregulate matrix metalloproteinases (MMPs). We examined whether enalapril affects MMP-2, MMP-8, and MMP-9 levels and activity, and their endogenous inhibitors (tissue inhibitors of MMPs, TIMP-1 and TIMP-2) levels in hypertensive patients. Moreover, we assessed the effects of enalaprilat on MMP-9 and TIMP-1 secretion by human endothelial cells (HUVECs). Thirty-eight hypertensive patients received enalapril for 8 weeks and were compared with thirty-eight normotensive controls. Blood samples were collected at baseline and after treatment. Plasma ACE activity was determined by a fluorimetric assay. Plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA and gelatin zymography. A fluorogenic peptide cleavage assay was used to measure MMP activity. HUVECs cells were stimulated by phorbol-12-myristate-13-acetate (PMA) and the effects of enalaprilat (10(-10) to 10(-6) M) on MMP-9 and TIMP-1 levels were determined. Enalapril decreased blood pressure and ACE activity in hypertensive patients (P < 0.05), but had no effects on plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 levels, or MMP activity. Enalaprilat had no effects on PMA-induced increases in MMP-9 and TIMP-1 secretion by HUVECs or on MMP activity. We show consistent evidence, both in vivo and in vitro, that enalapril does not affect MMPs and TIMPs levels in hypertensive patients.
Subject: ACE inhibitors
Matrix metalloproteinases
Editor: Springer
Citation: Cardiovascular Drugs and Therapy. Springer, v.26, n.6, p.511-519, 2012
Rights: fechado
Identifier DOI: 10.1007/s10557-012-6420-2
Date Issue: 2012
Appears in Collections:FCM - Artigos e Outros Documentos

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