title: Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure.
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 microM) 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.
authors.affiliation: Sezione di Anatomia Umana, Dipto. di Medicina Sperimentale, Università degli Studi di Palermo, Palermo, Italy. giampylr@hotmail.com
authors.forename: Giampiero
authors.initials: G
authors.lastname: La Rocca
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Stefano
authors.forename: Ermanno
authors.initials: E
authors.lastname: Eleuteri
authors.forename: Rita
authors.initials: R
authors.lastname: Anzalone
authors.forename: Francesca
authors.initials: F
authors.lastname: Magno
authors.forename: Simona
authors.initials: S
authors.lastname: Corrao
authors.forename: Tiziana
authors.initials: T
authors.lastname: Loria
authors.forename: Anna
authors.initials: A
authors.lastname: Martorana
authors.forename: Claudio
authors.initials: C
authors.lastname: Di Gangi
authors.forename: Marilena
authors.initials: M
authors.lastname: Colombo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Sansone
authors.forename: Francesco
authors.initials: F
authors.lastname: Patanè
authors.forename: Felicia
authors.initials: F
authors.lastname: Farina
authors.forename: Mauro
authors.initials: M
authors.lastname: Rinaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Giannuzzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zummo
mesh_terms: D002478:Cells, Cultured; D002908:Chronic Disease; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry; D009206:Myocardium / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D014471:Umbilical Veins
chemical_list: D016877:Oxidants; D012333:RNA, Messenger; D014443:Tyrosine; D006861:Hydrogen Peroxide; D009195:Peroxidase; C087259:3-chlorotyrosine