title: NOX5 expression is increased in intramyocardial blood vessels and cardiomyocytes after acute myocardial infarction in humans.
abstract: Reactive oxygen species producing NADPH oxidases play important roles under different (patho)physiological conditions. NOX1, NOX2, and NOX4 are important sources of reactive oxygen species in the heart, but knowledge of the calcium-dependent NOX5 in the heart is lacking. The presence of NOX5 was studied via RT-PCR in heart tissue from patients with end-stage heart failure; the tissue was obtained during cardiac transplantation surgery. NOX5 positivity and cellular localization were studied via IHC and digital-imaging microscopy in heart tissues of patients who did not have heart disease and in infarction areas of patients who died of myocardial infarctions of different durations. Furthermore, NOX5 expression was analyzed in vitro by using Western blot analysis. NOX5 RNA was found in the hearts of controls and patients with ischemic cardiomyopathy. In controls, NOX5 localized to the endothelium of a limited number of intramyocardial blood vessels and to a limited number of scattered cardiomyocytes. In infarcted hearts, NOX5 expression increased, especially in infarctions >12 hours, which manifested as an increase in NOX5-positive intramyocardial blood vessels, as well as in endothelium, smooth muscle, and cardiomyocytes. NOX5 was found in cardiomyocyte cytoplasm, plasma membrane, intercalated disks, and cross striations. Western blot analysis confirmed NOX5 expression in isolated human cardiomyocytes. For the first time to our knowledge, we demonstrate NOX5 expression in human intramyocardial blood vessels and cardiomyocytes, with significant increases in the affected myocardium after acute myocardial infarction.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. n.hahn@vumc.nl
authors.forename: Nynke E
authors.initials: NE
authors.lastname: Hahn
authors.forename: Christof
authors.initials: C
authors.lastname: Meischl
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Kawahara
authors.forename: René J P
authors.initials: RJ
authors.lastname: Musters
authors.forename: Viola M J
authors.initials: VM
authors.lastname: Verhoef
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
authors.forename: Alexander B A
authors.initials: AB
authors.lastname: Vonk
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
mesh_terms: D000368:Aged; D003331:Coronary Vessels / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006333:Heart Failure / Q000201:enzymology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D013737:Testis / Q000201:enzymology
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; C431571:NOX5 protein, human