Blood penetration into human aortic valves consecutive to endothelial micro-fissuring of the fibrosa determines the site of calcium deposition: Physiopathological implications
| Autor: | Fanny Perez, Marion Morvan, Dimitri Arangalage, Catherine Deschildre, David Messika-Zeitoun, Giuseppina Caligiuri, M.P. Jacob-Lenet, Christine Choqueux, G. Even, Antonino Nicoletti, L. Cattan-Levy, Michel Jb, Magnus Bäck, Isabelle Codogno, J. Laschet |
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| Rok vydání: | 2019 |
| Předmět: |
Pathology
medicine.medical_specialty biology medicine.diagnostic_test business.industry medicine.medical_treatment chemistry.chemical_element Calcium medicine.disease Immunofluorescence Red blood cell Hematoma medicine.anatomical_structure Valve replacement chemistry Aortic valve stenosis cardiovascular system Osteocalcin biology.protein Medicine Aortic valve calcification Cardiology and Cardiovascular Medicine business |
| Zdroj: | Archives of Cardiovascular Diseases Supplements. 11:106-107 |
| ISSN: | 1878-6480 |
| Popis: | Background Intraleaflet hematoma has been associated with advanced stages of aortic valve stenosis. Its presence is suspected to be involved in faster disease progression. However, the mechanism whereby the entry and the presence of blood elements into the valves would have an impact on the biology of aortic valvular interstitial cells (VICs) remains to be deciphered. Purpose To evaluate the presence of intraleaflet hematoma, in respect to calcium deposition, at all stages of aortic valve calcification (AC) and to assess its putative pathophysiologic implication. Methods The spatial relationship between calcium deposits and intraleaflet hematomas was analyzed by whole-mount staining of calcified and non-calcified human aortic valves, obtained in the context of heart transplantation and from patients who underwent surgical valve replacement. Endothelial micro-fissuring was evaluated by en face immunofluorescence and scanning electron microscope analyses of the fibrosa surface. Red blood cell preparations (RBCs) were used in vitro in order to assess, by immunofluorescence microscopy and Alizarin red staining, the potential impact of intraleaflet hematomas on the phenotype change of human VICs. Results Intraleaflet hematomas revealed by ferric iron deposits and extensive penetration of RBCs into the fibrosa, secondary to endothelial micro-fissuring, were found both in calcified and non-calcified valves. Primary VICs derived from non-calcified valves and cultured in the presence of senescent RBCs acquired an osteoblastic phenotype, as demonstrated by the production of osteocalcin and the formation of calcium deposits. Conclusions Intraleaflet hematomas occurring through endothelial micro-fissuring may play a critical role in the initiation of calcium deposition into human aortic valves by driving the acquisition of an osteoblastic phenotype by the VICs that enter in contact with the infiltrated RBCs. |
| Databáze: | OpenAIRE |
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