title: iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease.
abstract: Degenerative aortic stenosis (AS) is the most common worldwide cause of valve replacement. The aortic valve is a thin, complex, layered connective tissue with compartmentalized extracellular matrix (ECM) produced by specialized cell types, which directs blood flow in one direction through the heart. There is evidence suggesting remodeling of such ECM during aortic stenosis development. Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms. Aortic valve samples were collected from 18 patients which underwent aortic valve replacement (50% males, mean age of 74 years) and 18 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by 2D-LC MS/MS iTRAQ methodology. The results showed an altered expression of 13 ECM proteins of which 3 (biglycan, periostin, prolargin) were validated by Western blotting and/or SRM analyses. These findings are substantiated by our previous results demonstrating differential ECM protein expression. The present study has demonstrated a differential ECM protein pattern in individuals with AS, therefore supporting previous evidence of a dynamic ECM remodeling in human aortic valves during AS development.
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Martin-Rojas
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Mourino-Alvarez
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Alonso-Orgaz
authors.affiliation: Cardiocirculatory Unit, Health Research Institute, Hospital La Fe, Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Rosello-Lleti
authors.affiliation: Proteomics Core Facility, CNIC, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Cardiac Surgery, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Lopez-Almodovar
authors.affiliation: Cardiocirculatory Unit, Health Research Institute, Hospital La Fe, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.affiliation: Department of Cardiology, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Padial
authors.affiliation: Proteomics Core Facility, CNIC, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Lopez
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cuesta
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Barderas
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D040901:Proteomics
chemical_list: D016326:Extracellular Matrix Proteins