title: Negative feedback interaction of HO-1/INOS in PBMC of acute congestive heart failure patients.
abstract: Heart failure (HF) is a common clinical syndrome with frequent exacerbations requiring hospitalization. Among the various mechanisms that underlie the pathogenesis of HF, the activation of the immune system leads to a progressive and redundant release of proinflammatory cytokines responsible for a variety of deleterious effects in heart failure, such as endothelial dysfunction, apoptosis of myocytes, activation of MMPs (Matrix Metallo Proteinases) and oxidative stress, with the result of decreased inotropism and clinical syndrome such as pulmonary edema,. The condition of oxidative stress induces the expression of genes coding for the proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). Twenty-five hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction less than 35 percent) were included in the study. The aim of this study was to evaluate the cytokines plasma concentrations and the expression and activity of iNOS and HO-1 proteins in peripheral blood mononuclear cell (PBMC) extracted from patients in comparison to control group. In ACHF; left ventricular ejection fraction (LVEF) percent was reduced. Furthermore; iNOS and HO-1 expression and cytokines plasma levels were significantly higher in patients with ACHF as compared to controls group. Moreover the enzyme activity presents an opposite trend compared to that obtained in the analysis of the transcript and proteins. Our studies suggest a negative feedback interaction between iNOS and HO-1 important in the physiopathology of heart failure that could be considered a good candidate as a future therapeutic target for the development of new drugs.
authors.affiliation: Department of Medicine and Science of Aging, University G. d' Annunzio, Chieti, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Speranza
authors.forename: S
authors.initials: S
authors.lastname: Franceschelli
authors.forename: M
authors.initials: M
authors.lastname: Pesce
authors.forename: A
authors.initials: A
authors.lastname: Ferrone
authors.forename: A
authors.initials: A
authors.lastname: Patruno
authors.forename: G
authors.initials: G
authors.lastname: Riccioni
authors.forename: M A
authors.initials: MA
authors.lastname: De Lutiis
authors.forename: M
authors.initials: M
authors.lastname: Felaco
authors.forename: A
authors.initials: A
authors.lastname: Grilli
mesh_terms: D000208:Acute Disease; D000368:Aged; D025461:Feedback, Physiological; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D016277:Ventricular Function, Left
chemical_list: D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1