Titel: Sphingosine 1-phosphate receptors and selected cell markers in aneurysmatic and dissected tissue from the human infrarenal abdominal aorta
Sonstige Titel: Sphingosin-1-phosphat Rezeptoren und ausgewählte Zellmarker in Aneurysma- und Dissektionsgewebe in der humanen infrarenalen Aorta abdominalis
Sprache: Englisch
Autor*in: Michaels, Louisa
Schlagwörter: Sphingosine-1 phosphate; Glatte Muskelzelldegeneration; endotheliale Dysfunktion
GND-Schlagwörter: AneurysmaGND
Erscheinungsdatum: 2021
Tag der mündlichen Prüfung: 2023-03-06
Aneurysm, dissection, and atherosclerosis are vascular diseases that can also arise in the abdominal aorta (AA). Due to high prevalence and high mortality rates, they are worldwide of concern. Detailed cellular pathomechanisms have not been fully elucidated and drug therapy as well as preventive strategies are still lacking.
This study investigated associations of the expression of cell markers, vascular genes and S1P receptors (S1PR) with the named AA pathologies. AA tissue specimens (N = 95) were harvested during autopsies from people that had suffered a dissection or aneurysm in any aortic section. Analyses of the expression of selected genes was performed by RT-qPCR and in addition, selected tissues were stained for macrophages.
Our data support the assumption that AA aneurysms arise as a complication of atherosclerosis in the AA. In the pathogenesis of dissection, atherosclerosis appeared less critical. For all pathologies, downregulation of VSMC differentiation marker Myh11 was observed indicating a loss of differentiated VSMCs due to phenotypic change and cell death. Expression levels of histone-deacetylase SIRT1 were found to correlate to those of Myh11, suggesting a functional link between SIRT1 loss and VSMC dedifferentiation in aortic pathologies. Surprisingly, expression of macrophage marker CD68 was not significantly altered in any of the pathology subgroups. Staining of selected tissues with the macrophage marker Mac2 showed macrophages accumulating in the intima and in plaque areas in tissue samples from aneurysm and atherosclerosis. In dissected tissues macrophages were also found in the medial layer and around dissection edges. S1PRs are critical in vascular development and homeostasis, however their cell-specific role in the named aortic pathologies has not been studied yet. Here, we show a significant decrease of S1PR2 and S1PR3 expression in aneurysm and atherosclerosis. The loss of S1PR2 might well contribute to the dedifferentiation of VSMCs, as S1PR2/RhoA signaling is known to promote the expression of VSMC differentiation genes. Our data may suggest the existence of a S1PR2/SIRT1 axis in VSMCs that may regulate atherosclerosis and aneurysm in the AA. Future work may define the potential of S1P receptor agonism or antagonism for pharmacological treatment of AA pathologies.
URL: https://ediss.sub.uni-hamburg.de/handle/ediss/10147
URN: urn:nbn:de:gbv:18-ediss-107775
Dokumenttyp: Dissertation
Betreuer*in: Larena-Avellaneda, Axel Antonio
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen

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