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- Title
Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient.
- Authors
Millucci, Lia; Ghezzi, Lorenzo; Paccagnini, Eugenio; Giorgetti, Giovanna; Viti, Cecilia; Braconi, Daniela; Laschi, Marcella; Geminiani, Michela; Soldani, Patrizia; Lupetti, Pietro; Orlandini, Maurizio; Benvenuti, Chiara; Perfetto, Federico; Spreafico, Adriano; Bernardini, Giulia; Santucci, Annalisa
- 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 froman 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 fromrheumatoid 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.
- Subjects
AMYLOIDOSIS; OXIDATIVE stress; INFLAMMATION; METABOLIC syndrome; ALKAPTONURIA; DIOXYGENASES
- Publication
Mediators of Inflammation, 2014, Vol 2014, p1
- ISSN
0962-9351
- Publication type
Article
- DOI
10.1155/2014/258471