Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure |
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Authors: | Dr Giampiero La Rocca Antonino Di Stefano Ermanno Eleuteri Rita Anzalone Francesca Magno Simona Corrao Tiziana Loria Anna Martorana Claudio Di Gangi Marilena Colombo Fabrizio Sansone Francesco Patanè Felicia Farina Mauro Rinaldi Francesco Cappello Pantaleo Giannuzzi Giovanni Zummo |
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Institution: | 1. Sezione di Anatomia Umana, Dipto. di Medicina Sperimentale, Università degli Studi di Palermo, Via del Vespro 129, 90127, Palermo, Italy 2. Laboratorio di Citoimmunopatologia Apparato Cardio-Respiratorio, Fondazione S. Maugeri, IRCCS, Veruno, NO, Italy 3. Divisione di Cardiologia, Fondazione S. Maugeri, IRCCS, Veruno, NO, Italy 4. Dipto. di Patologia Umana, Università degli Studi di Palermo, Palermo, Italy 5. Istituto di Ostetricia e Ginecologia, Università degli Studi di Palermo, Palermo, Italy 6. Divisione di Cardiochirurgia, Ospedale S. Giovanni Battista, Turin, Italy
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Abstract: | Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings
suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by
contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may
lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells
(EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected
to oxidative stress by incubation with hydrogen peroxide at non lethal (60 μM) dose for different exposure times (3 and 6 h).
Treated and control cells were tested by immunohistochemistry and RT-PCR for MPO and 3-chlorotyrosine expression. Both endothelial
cell types expressed myeloperoxidase following oxidative stress, with higher levels in EEC. Moreover, 3-chlorotyrosine accumulation
in treated cells alone indicated the presence of MPO-derived hypochlorous acid. Immunohistochemistry on sections from post-infarcted
heart confirmed in vivo the endothelial positivity to MPO, 3-chlorotyrosine and, to a minor extent, nitrotyrosine. Immunohistochemical
observations were confirmed by detection of MPO mRNA in both stimulated EEC and HUVEC cells. This study demonstrates for the
first time that EEC can express MPO after oxidative stress, both in vitro and in vivo, followed by accumulation of 3-chlorotyrosine,
an end product of oxidative stress. Deregulation of endothelial functions may contribute to the development of a number of
cardiovascular diseases, including CHF. The results also highlight the notion that endothelium is not only a target but also
a key player in oxidative-driven cardiovascular stress.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.
G. La Rocca and A. Di Stefano contributed equally to the current work.
Returned for 1. Revision: 7 January 2008 1. Revision received: 18 June 2008
Returned for 2. Revision: 17 July 2008 2. Revision received: 17 October 2008 |
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Keywords: | 3-chlorotyrosine endocardium endothelial cells myeloperoxidase oxidative stress |
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