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https://hdl.handle.net/123456789/1865| Τύπος: | Ανακοίνωση σε συνέδριο |
| Τίτλος: | Improved rabbit model of calcific aortic valve disease induces severe medial calcification and stenosis equivalent to human disease |
| Συγγραφέας: | [EL] Ανουσάκης - Βλαχοχρήστου, Νίκος[EN] Anousakis - Vlachochristou, Nikolaos [EL] Μαυροειδής, Εμμανουήλ[EN] Mavroidis, Manolis [EL] Αθανασιάδου, Δήμητρα[EN] Athanasiadou, Dimitra [EL] Βαρελά, Αιμιλία[EN] Varela, Aimilia [EL] Μακρυδάκης, Μανούσος[EN] Makridakis, Manousos [EL] Κάτσα, Μαρία[EN] Katsa, Maria [EL] Μήλιου, Αντιγόνη[EN] Miliou, Antigoni [EL] Λαλή, Δήμητρα[EN] Lali, Dimitra [EN] Carneiro, Karina M.M. [EL] Βλάχου, Αντωνία[EN] Vlahou, Antonia [EL] Θωμαΐδης, Νικόλαος[EN] Thomaidis, Nikolaos [EL] Αναγνωστόπουλος, Κωνσταντίνος[EN] Anagnostopoulos, Constantinos [EL] Κόκκινος, Διονύσιος[EN] Cokkinos, Dionysios [EL] Τσιούφης, Κωνσταντίνος[EN] Tsioufis, Costas [EL] Τούτουζας, Κωνσταντίνος[EN] Toutouzas, Konstantinos |
| Ημερομηνία: | 08/11/2021 |
| Περίληψη: | Introduction: Accurate animal models of calcific aortic valve stenosis (CAVS) are needed to get insights into the early stages. We had previously modified a rabbit model to achieve CAVS. Here, we sought to assess its ability to produce similar lesion to humans. Methods: New Zealand rabbits were randomized to normal diet or +1% cholesterol + 3500 I.U.s/kg Vitamin D2 daily. Aortic valve area was assessed with echocardiography. At 7 weeks, blood serum and valve cusps were retrieved from sacrificed animals. Valve cusps were ex-vivo imaged with 18F-NaF microPET/CT, snap-frozen or formalin-fixed. Cusps were homogenized with an optimized protocol. Pyrophosphate (PPi) was measured in serum and cusps, metabolites analyzed with LC-MS/MS. Phosphatase activity was detected with BCIP/NBT assay. Protein content was analyzed with immunohistochemistry, quantitative ELISA and proteomics analysis (LC-MS/MS), and compared to human databases. Fixed cusps were analyzed using FT-IR and imaged with atomic force, scanning and transmission electron microscope. EDX chemical maps were obtained from the regions of interest Results: Vitamin D and metabolites were validated in serum and tissue. Echocardiography confirmed significant valve stenosis. Sodium fluoride activity was quadrupled in experimental valves. Histology revealed severe medial calcification, positive for osteopontin, negative for TNAP, BSPII and osteocalcin. Endogenous phosphatase activity colocalized with calcification in the medium. Serum PPi levels were increased, and tissue PPi levels were decreased. Proteomics analysis revealed 96 differentially expressed proteins validating important proteins, including apolipoproteins, complement, osteonectin, matrix Gl(a), galectin-3, fetuin-A, sortiltin, and TGF-b axis proteins. Ultrastructural analysis revealed the pathognomonic calcified spherical particles composed predominantly of phosphorus in the experimental valves. Conclusions: The improved high-fat - vitamin D toxicity rabbit model produced severe phosphate-induced CAVS, with similar protein and ultrastructural content to human disease, related to TGF-b pathway. Further investigations are needed in the underlying molecular networks driving the lesion. |
| Γλώσσα: | Αγγλικά |
| Τόπος δημοσίευσης: | Βοστώνη, ΗΠΑ |
| Σελίδες: | 2 |
| DOI: | 10.1161/circ.144.suppl_1.13262 |
| EISSN: | 1524-4539 |
| Θεματική κατηγορία: | [EL] Επιστήμες υγείας, άλλοι τομείς[EN] Health sciences, miscellaneous |
| Κάτοχος πνευματικών δικαιωμάτων: | © The Author(s) 2021 |
| Ηλεκτρονική διεύθυνση του τεκμηρίου στον εκδότη: | https://www.ahajournals.org/doi/10.1161/circ.144.suppl_1.13262 |
| Ηλεκτρονική διεύθυνση περιοδικού: | https://www.ahajournals.org/journal/circ |
| Τίτλος πηγής δημοσίευσης: | Circulation |
| Τεύχος: | Suppl_1 |
| Τόμος: | 144 |
| Σελίδες τεκμηρίου (στην πηγή): | Article no 13262 |
| Όνομα εκδήλωσης: | American Heart Association Scientific Sessions 2021 |
| Τοποθεσία εκδήλωσης: | Boston, USA |
| Ημ/νία έναρξης εκδήλωσης: | 13/11/2021 |
| Ημ/νία λήξης εκδήλωσης: | 15/11/2021 |
| Εμφανίζεται στις συλλογές: | Ερευνητικές ομάδες |
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