title: Human Ischemic Cardiomyopathy Shows Cardiac Nos1 Translocation and its Increased Levels are Related to Left Ventricular Performance.
abstract: The role of nitric oxide synthase 1 (NOS1) as a major modulator of cardiac function has been extensively studied in experimental models; however, its role in human ischemic cardiomyopathy (ICM) has never been analysed. Thus, the objectives of this work are to study NOS1 and NOS-related counterparts involved in regulating physiological function of myocyte, to analyze NOS1 localisation, activity, dimerisation, and its relationship with systolic function in ICM. The study has been carried out on left ventricular tissue obtained from explanted human hearts. Here we demonstrate that the upregulation of cardiac NOS1 is not accompanied by an increase in NOS activity, due in part to the alterations found in molecules involved in the regulation of its activity. We observed partial translocation of NOS1 to the sarcolemma in ischemic hearts, and a direct relationship between its protein levels and systolic ventricular function. Our findings indicate that NOS1 may be significant in the pathophysiology of human ischemic heart disease with a preservative role in maintaining myocardial homeostasis.
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-Lletí
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford, United Kingdom.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carnicer
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gil-Cayuela
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: Jose Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012508:Sarcolemma / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods; D015854:Up-Regulation; D016277:Ventricular Function, Left
chemical_list: C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I