title: Nitric oxide synthetic pathway in patients with microvascular angina and its relations with oxidative stress.
abstract: A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs) participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis.
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Porro
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Eligini
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy ; Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, 20138 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lualdi
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Squellerio
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Susanna
authors.identifier: 0000-0002-4106-0128
authors.initials: S
authors.lastname: Fiorelli
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Giovannardi
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Chiorino
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Dalla Cia
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Crisci
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy.
authors.forename: José Pablo
authors.initials: JP
authors.lastname: Werba
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy ; Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S., 20138 Milan, Italy ; Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, 20138 Milan, Italy.
authors.forename: Viviana
authors.identifier: 0000-0003-1349-8365
authors.initials: V
authors.lastname: Cavalca
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000032:analysis*; D006801:Humans; D008297:Male; D017566:Microvascular Angina / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D053719:Tandem Mass Spectrometry
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D005978:Glutathione