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https://hdl.handle.net/123456789/1866| Τύπος: | Ανακοίνωση σε συνέδριο |
| Τίτλος: | Extracellular glycoproteins and advanced glycation end products associate with calcification development in human and rabbit calcified aortic valves |
| Συγγραφέας: | [EL] Ανουσάκης - Βλαχοχρήστου, Νίκος[EN] Anousakis - Vlachochristou, Nikolaos [EL] Αθανασιάδου, Δήμητρα[EN] Athanasiadou, Dimitra [EL] Μαυροειδής, Εμμανουήλ[EN] Mavroidis, Manolis [EL] Μήλιου, Αντιγόνη[EN] Miliou, Antigoni [EL] Μακρυδάκης, Μανούσος[EN] Makridakis, Manousos [EL] Κακλαμάνης, Λουκάς[EN] Kaklamanis, Loucas [EL] Αδαμόπουλος, Σταμάτης[EN] Adamopoulos, Stamatis [EL] Βλάχου, Αντωνία[EN] Vlahou, Antonia [EL] Κόκκινος, Διονύσιος[EN] Cokkinos, Dionysios [EN] Carneiro, Karina M.M. [EL] Τούτουζας, Κωνσταντίνος[EN] Toutouzas, Konstantinos |
| Ημερομηνία: | 08/05/2022 |
| Περίληψη: | Background Aortic valve stenosis (AS) remains without pharmaceutical therapy. Infrared spectroscopy (IR) has demonstrated increased valve glycosylation, possibly by the formation of oxidation-mediated advanced glycation end products (AGEs). Here, we investigate whether AGEs are increased in non-diabetic patients and a validated AS rabbit model. Methods Ten AS patients with Diabetes Mellitus (DM), 10 without DM undergoing valve replacement, and 10 patients undergoing heart transplantation with healthy valves were studied. Also, 12 rabbits, randomized to normal diet vs diet supplemented with 1% cholesterol and 3500 IUs/kg Vitamin D daily for 7 weeks, were examined. Cusps were snap-frozen, homogenized, and total AGEs were measured with quantitative ELISA. Protein analysis of homogenates was performed with LC-MS/MS. Cryosections were methanol-acetone fixed and stained with calcein. Glycosylation autofluorescence and calcification were imaged with confocal microscopy (Leica SP5, 405, 488 nm lasers), and average intensity/volume was calculated. Animal valve cusps were formalin-fixed, critical point dried, and analyzed with IR (Thermo Scientific FTIR Nicolet iS20). Results DM patients demonstrated increased calcification compared to non-DM patients. Non-DM patients showed similar glycation autofluorescence signal compared to controls, and DM patients disclosed reduced glycation autofluorescence versus controls. Total AGEs were increased only in human DM cusps. Mass spectrometry, among 96 differentially expressed proteins, revealed 41 overexpressed glycoproteins in rabbits, of these 16 were extracellular matrix-bound, including vintronectin (ratio: x3.05), fibronectin (x4.1), fetuin-a (x6.7), and osteonectin (experimental cusps only). Spectroscopic analysis revealed peaks of increased intensity within the range 1000-1200 cm-1 in animal calcified vs control valves, in the same region with fetuin-a spectrum. Conclusion AGEs are increased in AS patients with DM and correlated with calcification, but not in non-DM patients. Extracellular matrix glycoproteins, importantly fetuin-a, are significantly increased in rabbit valves, similar to human disease. |
| Γλώσσα: | Αγγλικά |
| Τόπος δημοσίευσης: | Washington, DC USA |
| Σελίδες: | 1 |
| DOI: | 10.1016/S0735-1097(22)02677-8 |
| EISSN: | 1558-3597 |
| Θεματική κατηγορία: | [EL] Επιστήμες υγείας, άλλοι τομείς[EN] Health sciences, miscellaneous |
| Κάτοχος πνευματικών δικαιωμάτων: | © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
| Ηλεκτρονική διεύθυνση του τεκμηρίου στον εκδότη: | https://www.sciencedirect.com/science/article/pii/S0735109722026778 |
| Ηλεκτρονική διεύθυνση περιοδικού: | https://www.sciencedirect.com/journal/journal-of-the-american-college-of-cardiology |
| Τίτλος πηγής δημοσίευσης: | Journal of the American College of Cardiology |
| Τεύχος: | 9, Supplement |
| Τόμος: | 79 |
| Σελίδες τεκμηρίου (στην πηγή): | 1686 |
| Όνομα εκδήλωσης: | 71st Annual Scientific Session |
| Τοποθεσία εκδήλωσης: | Washington, DC United States |
| Ημ/νία έναρξης εκδήλωσης: | 02/04/2022 |
| Ημ/νία λήξης εκδήλωσης: | 04/04/2022 |
| Εμφανίζεται στις συλλογές: | Ερευνητικές ομάδες |
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