title: Patients with calcific aortic stenosis exhibit systemic molecular evidence of ischemia, enhanced coagulation, oxidative stress and impaired cholesterol transport.
abstract: BACKGROUND
  The most common valve diseases are calcific aortic stenosis (AS) and aortic regurgitation (AR). The former is characterized by thickening of valve leaflets followed by progressive calcification, which produces progressive aortic valve (AV) narrowing, increased pressure afterload on the left ventricle (LV) and subsequent LV hypertrophy. On the other hand, AR is due to malcoaptation of the valve leaflets with resultant diastolic reflux of blood from aorta back to the LV producing volume and pressure overload and progressive LV dilatation. In order to isolate the molecular mechanisms taking place during AS, we have used an integrated "-omic" approach to compare plasma samples from AS and from AR patients used as controls. The final purpose of this work is to find molecular changes in response to the calcification of the AV, diminishing the effects of the AV dysfunction.
  
  
  RESULTS
  Using two-dimensional difference gel electrophoresis (2D-DIGE) and gas chromatography coupled to mass spectrometry (GC-MS) in a cohort of 6 subjects, we have found differences in 24 protein spots and 19 metabolites, respectively. Among them, 7 proteins and 3 metabolites have been verificated by orthogonal techniques (SRM or turbidimetry): fibrinogen beta and gamma chain, vitronectin, apolipoprotein C-II, antithrombin III, haptoglobin, succinic acid, pyroglutamic acid and alanine. Classification according to their main function showed alterations related to coagulation, inflammation, oxidative stress, response to ischemia and lipid metabolism, defining 4 different molecular panels that characterize AS with high specificity and sensitivity.
  
  
  CONCLUSIONS
  These results may facilitate management of these patients by making faster diagnostics of the disease and better understand these pathways for regulating its progression.
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: Montserrat
authors.initials: M
authors.lastname: Baldan-Martin
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez-Calero
authors.affiliation: Seralab, Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martinez-Laborde
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: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Luna
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: Department of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernandez-Aviles
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Vivanco
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: Akerstrom
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Alvarez-Llamas
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. Electronic address: megonzalezb@sescam.jccm.es.
authors.forename: María G
authors.initials: MG
authors.lastname: Barderas
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D001777:Blood Coagulation / Q000502:physiology*; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D040901:Proteomics / Q000379:methods
chemical_list: D002784:Cholesterol
keywords: Aortic regurgitation; Calcific aortic stenosis; Calcification; Metabolomics; Proteomics