Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Karageorgiadi Dimitra
Dissertation committee:
Ζωγράφος Γεώργιος, Καθηγητής Χειρουργικής, Ιατρική Σχολή, ΕΚΠΑ
Σιγάλα Φραγκίσκα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπουσα
Φίλης Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αλεξάκης Νικόλαος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ανδρεάδου Ιωάννα, Καθηγήτρια, Φαρμακευτική Σχολή, ΕΚΠΑ
Πατέρας Ιωάννης, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παπαλάμπρος Αλέξανδρος-Λουκάς, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μελέτη των μοριακών μηχανισμών της ισχαιμικής και της μετισχαιμικής προστασίας σε όργανα στόχους μετά από υπερνεφρικό αποκλεισμό της κοιλιακής αορτής σε αρουραίους
Translated title:
Study of molecular mechanism of ischemic conditioning to target organs after suprarenal occlusion of the abdominal aorta in rats.
Summary:
Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p<0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocked key protective signaling routes, abrogating the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-β1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-β1 as an attractive target for manipulation in this context.
Main subject category:
Health Sciences
Keywords:
Ischemic conditioning, Abdominal aortic aneurysm (AAA), Molecular mechanisms
Number of references:
185
