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Type: Artigo de periódico
Title: Antioxidant treatment protects against matrix metalloproteinase activation and cardiomyocyte injury during acute pulmonary thromboembolism
Author: Sousa-Santos, Ozelia
Neto-Neves, Evandro M.
Ferraz, Karina C.
Ceron, Carla S.
Rizzi, Elen
Gerlach, Raquel F.
Tanus-Santos, Jose E.
Abstract: Increased reactive oxygen species (ROS) promote matrix metalloproteinase (MMP) activities and may underlie cardiomyocyte injury and the degradation of cardiac troponin I (cTI) during acute pulmonary thromboembolism (APT). We examined whether pretreatment or therapy with tempol (a ROS scavenger) prevents MMP activation and cardiomyocyte injury of APT. Anesthetized sheep received tempol infusion (1.0 mg kg(-1) min(-1), i.v.) or saline starting 30 min before or 30 min after APT (autologous blood clots). Control animals received saline. Hemodynamic measurements were performed. MMPs were studied in the right ventricle (RV) by gelatin zymography, fluorimetric activity assay, and in situ zymography. The ROS levels were determined in the RV and cTI were measured in serum samples. APT increased the pulmonary arterial pressure and pulmonary vascular resistance by 146 and 164 %, respectively. Pretreatment or therapy with tempol attenuated these increases. While APT increased RV + dP/dt (max), tempol infusions had no effects. APT increased RV MMP-9 (but not MMP-2) levels. In line with these findings, APT increased RV MMP activities, and this finding was confirmed by in situ zymography. APT increased the RV ROS levels and tempol infusion, before or after APT, and blunted APT-induced increases in MMP-9 levels, MMP activities, in situ MMP activities, and ROS levels in the RV. cTI concentrations increased after APT, and tempol attenuated these increases. RV oxidative stress after APT increases the RV MMP activities, leading to the degradation of sarcomeric proteins, including cTI. Antioxidant treatment may prevent MMP activation and protect against cardiomyocyte injury after APT.
Subject: Antioxidant
Cardiomyocyte injury
Cardiac troponin I
Matrix metalloproteinases
Reactive oxygen species
Editor: Springer
Citation: Naunyn-Schmiedebergs Archives of Pharmacology. Springer, v.385, n.7, p.685-696, 2012
Rights: fechado
Identifier DOI: 10.1007/s00210-012-0748-9
Date Issue: 2012
Appears in Collections:FCM - Artigos e Outros Documentos

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