title: MALDI-Imaging Mass Spectrometry: a step forward in the anatomopathological characterization of stenotic aortic valve tissue.
abstract: Aortic stenosis (AS) is the most common form of valve disease. Once symptoms develop, there is an inexorable deterioration with a poor prognosis; currently there are no therapies capable of modifying disease progression, and aortic valve replacement is the only available treatment. Our goal is to study the progression of calcification by matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) and get new insights at molecular level that could help in the understanding of this disease. In this work, we analyzed consecutive slices from aortic valve tissue by MALDI-IMS, to establish the spatial distribution of proteins and peptides directly from the surface of the histological sections. The analysis showed different structures corresponding to regions observed in conventional histology, including large calcification areas and zones rich in collagen and elastic fibers. Peptide extraction from the tissue, followed by liquid chromatography mass spectrometry analysis, provided the identification of collagen VI α-3 and NDRG2 proteins which correlated with the masses obtained by MALDI-IMS and were confirmed by immunohistochemistry. These results highlighted the molecular mechanism implied in AS using MALDI-IMS, a novel technique never used before in this pathology. In addition, we can define specific regions proving a complementary resolution of the molecular histology.
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: Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain.
authors.forename: Ibon
authors.initials: I
authors.lastname: Iloro
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: Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain.
authors.forename: Mikel
authors.initials: M
authors.lastname: Azkargorta
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Sastre-Oliva
authors.affiliation: Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain.
authors.forename: Iraide
authors.initials: I
authors.lastname: Escobes
authors.affiliation: Cardiac Surgery, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Lopez-Almodovar
authors.affiliation: Department of Cardiology, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.|Department of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Sanchez
authors.affiliation: IDEKO-IK4, Arriaga Industrialdea, Elgoibar, Spain.
authors.forename: Harkaitz
authors.initials: H
authors.lastname: Urreta
authors.affiliation: Department of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernandez-Aviles
authors.affiliation: Cardiac Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Pinto
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: Department of Cardiology, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Finn
authors.initials: F
authors.lastname: Akerström
authors.affiliation: Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Elortza
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: D000369:Aged, 80 and over; D001021:Aortic Valve / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008867:Microtomy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D016610:Tissue Embedding; D065467:Transcatheter Aortic Valve Replacement; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024142:Collagen Type VI; C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins