title: Amyloidosis, inflammation, and oxidative stress in the heart of an alkaptonuric patient.
abstract: BACKGROUND
  Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient.
  
  
  RESULTS
  Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient.
  
  
  CONCLUSIONS
  SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Lia
authors.identifier: 0000-0002-5379-8808
authors.initials: L
authors.lastname: Millucci
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghezzi
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Eugenio
authors.identifier: 0000-0002-9784-2057
authors.initials: E
authors.lastname: Paccagnini
authors.affiliation: Dipartimento di Scienze Fisiche, della Terra e dell'Ambiente, Università degli Studi di Siena, Via Laterina, 53100 Siena, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgetti
authors.affiliation: Dipartimento di Scienze Fisiche, della Terra e dell'Ambiente, Università degli Studi di Siena, Via Laterina, 53100 Siena, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Viti
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Daniela
authors.identifier: 0000-0002-9657-4169
authors.initials: D
authors.lastname: Braconi
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Marcella
authors.identifier: 0000-0002-2736-4010
authors.initials: M
authors.lastname: Laschi
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Geminiani
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Soldani
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Lupetti
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Maurizio
authors.identifier: 0000-0002-6112-4889
authors.initials: M
authors.lastname: Orlandini
authors.affiliation: Medicina e Riattivazione Cardiologica DAI Cuore e Vasi, AOU Careggi, 50139 Firenze, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Benvenuti
authors.affiliation: Centro di Riferimento Regionale per lo Studio dell'Amiloidosi, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Viale Pieraccini 18, 50139 Firenze, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Perfetto
authors.affiliation: Immunoematologia Trasfusionale, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, 53100 Siena, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Spreafico
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Giulia
authors.identifier: 0000-0003-0016-0728
authors.initials: G
authors.lastname: Bernardini
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000368:Aged; D000474:Alkaptonuria / Q000276:immunology* / Q000378:metabolism*; D000686:Amyloidosis / Q000503:physiopathology*; D001021:Aortic Valve / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D009206:Myocardium / Q000378:metabolism; D009794:Ochronosis / Q000378:metabolism; D018384:Oxidative Stress; D000685:Serum Amyloid A Protein / Q000378:metabolism
chemical_list: D000685:Serum Amyloid A Protein