title: Platelet activation and arterial peripheral serotonin turnover in cardiac remodeling associated to aortic stenosis.
abstract: Peripheral serotonin (5-HT) has been involved in adverse cardiac remodeling and valve fibrosis. The peripheral levels of 5-HT mainly depend on its release from activated platelets and degradation by monoamine oxidase A (MAO-A). The SERAOPI study investigated the relationship between arterial serotoninergic system, degree of platelet activation and cardiac remodeling, in patients with aortic valve stenosis (AS). Thirty patients with severe AS and 15 control subjects underwent transthoracic echocardiography, radial, and aortic arterial blood sampling. Measurements of 5-HT and its MAO-A-dependent degradation product, 5-HIAA, were performed by HPLC. Arterial platelet activation was assessed by flow cytometry analysis of platelet surface expression of P-selectin and activated integrin GPIIb/IIIa. Activated platelets and arterial plasma 5-HT increased in AS patients as compared to control subjects (P-selectin 1.08 ± 0.2MFI vs. 0.49 ± 0.1MFI, P = 0.04; GPIIb/IIIa 0.71 ± 0.1MFI vs. 0.35 ± 0.1MFI; P = 0.0015 and arterial plasma 5-HT 11.55 ± 1.6 nM vs. 6.18 ± 0.7 nM, P = 0.028, respectively). Moreover, 5-HT was strongly correlated to left ventricular hypertrophy assessed by echocardiography. The correlation was independent of cardiovascular risk comorbidities and others echocardiographic AS parameters. Finally, plasma 5-HIAA increased in AS patients (74.64 ± 9.7 nM vs. 37.16 ± 4.1 nM; P = 0.0002) indicating a higher 5-HT degradation rate by MAO-A. Platelet activation, arterial circulating serotonin, and serotonin degradation increased in patients with AS. These observations suggest that the serotoninergic system may contribute to the pathogenesis of AS including valve fibrosis and adverse ventricular remodeling.
authors.affiliation: INSERM, I2MC, U1048 Toulouse, Team 6 and 11, Institut des Maladies Métaboliques et Cardiovasculaires, 1 avenue Jean Poulhès, BP 84225, Toulouse Cedex 4, France; Department of Pharmacy, University Hospital Toulouse, Hôpital Paule de Viguier, 330 Avenue de Grande-Bretagne, TSA 70034, Toulouse Cedex 9, France; Unit of Pharmacology, University Hospital Versailles, Service de Biologie Médicale, Unité de Pharmacologie-Toxicologie, Hôpital A. Mignot, 177 Rue de Versailles, Le Chesnay, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rouzaud-Laborde
authors.forename: Clément
authors.initials: C
authors.lastname: Delmas
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pizzinat
authors.forename: Florence
authors.initials: F
authors.lastname: Tortosa
authors.forename: Cédric
authors.initials: C
authors.lastname: Garcia
authors.forename: Jeanne
authors.initials: J
authors.lastname: Mialet-Perez
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.forename: Pierre
authors.initials: P
authors.lastname: Sié
authors.forename: Odile
authors.initials: O
authors.lastname: Spreux-Varoquaux
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sallerin
authors.forename: Didier
authors.initials: D
authors.lastname: Carrié
authors.forename: Michel
authors.initials: M
authors.lastname: Galinier
authors.forename: Angelo
authors.initials: A
authors.lastname: Parini
authors.forename: Olivier
authors.initials: O
authors.lastname: Lairez
mesh_terms: D001024:Aortic Valve Stenosis / Q000097:blood* / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004452:Echocardiography; D015150:Echocardiography, Doppler; D005434:Flow Cytometry; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008875:Middle Aged; D015539:Platelet Activation; D017534:Radial Artery; D012701:Serotonin / Q000097:blood*; D020257:Ventricular Remodeling; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D014841:von Willebrand Factor; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid