TY  - THES
A1  - Eckner, Georg Ludwig
T1  - Der Einfluss vaskulär-adventitieller Makrophagen auf Gefäßwand-residente Stammzellen
T1  - The influence of vascular-adventitial macrophages on vessel wall resident stem cells
N2  - In dieser Dissertation wurden murine Aorta-Explantate im experimentellen Ansatz des "Aortic Ring Assay" über elf Tage kultiviert, erstmalig die Differenzierung zu F4/80(+)-Makrophagen gezeigt und eine nahezu vollständige Depletion dieser Zellen durch Clodronat-Liposomen bewirkt. Diese Adventitia-generierten Makrophagen wurden als die Hauptquelle des lokal gebildeten VEGF nachgewiesen. Die daraus resultierende Depletion des parakrin wirkenden VEGF resultierte in einer teilweisen Konservierung der CD34(+) „Vaskulogenen Zone“ der aortalen Adventitia. Zu der Bestätigung dieser Ergebnisse wurde experimentell über den VEGF-Rezeptor-Blocker E7080 in das VEGF-VEGFR-2 System eingegriffen. Die Versuchsansätze mit diesem Rezeptorblocker resultierten in einem ähnlichen Ergebnis wie die Versuche unter Makrophagen-Depletion.
N2  - In this dissertation murine aortic explants were cultivated for eleven days, using the method of “Aortic Ring Assay”. For the first time the differentiation to F4/80(+) macrophages and its depletion via clodronate liposomes could be described. These adventitia derived macrophages were identified to be the main source of the local VEGF. The depletion resulted in a lack of paracrine operating VEGF, thus partly preserving the CD34(+) vasculogenic zone within the aortal adventitia. To confirm these findings the VEGF-Receptor was blocked due to the VEGF-Receptor blocker E7080. These experiments resulted in almost the same findings compared to macrophage depletion.
KW  - Gefäßwand
KW  - Adventitia
KW  - Makrophagen
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206080
ER  - 
TY  - JOUR
A1  - Kleefeldt, Florian
A1  - Upcin, Berin
A1  - Bömmel, Heike
A1  - Schulz, Christian
A1  - Eckner, Georg
A1  - Allmanritter, Jan
A1  - Bauer, Jochen
A1  - Braunger, Barbara
A1  - Rueckschloss, Uwe
A1  - Ergün, Süleyman
T1  - Bone marrow-independent adventitial macrophage progenitor cells contribute to angiogenesis
JF  - Cell Death & Disease
N2  - Pathological angiogenesis promotes tumor growth, metastasis, and atherosclerotic plaque rupture. Macrophages are key players in these processes. However, whether these macrophages differentiate from bone marrow-derived monocytes or from local vascular wall-resident stem and progenitor cells (VW-SCs) is an unresolved issue of angiogenesis. To answer this question, we analyzed vascular sprouting and alterations in aortic cell populations in mouse aortic ring assays (ARA). ARA culture leads to the generation of large numbers of macrophages, especially within the aortic adventitia. Using immunohistochemical fate-mapping and genetic in vivo-labeling approaches we show that 60% of these macrophages differentiate from bone marrow-independent Ly6c\(^{+}\)/Sca-1\(^{+}\) adventitial progenitor cells. Analysis of the NCX\(^{−/-}\) mouse model that genetically lacks embryonic circulation and yolk sac perfusion indicates that at least some of those progenitor cells arise yolk sac-independent. Macrophages represent the main source of VEGF in ARA that vice versa promotes the generation of additional macrophages thereby creating a pro-angiogenetic feedforward loop. Additionally, macrophage-derived VEGF activates CD34\(^{+}\) progenitor cells within the adventitial vasculogenic zone to differentiate into CD31\(^{+}\) endothelial cells. Consequently, depletion of macrophages and VEGFR2 antagonism drastically reduce vascular sprouting activity in ARA. In summary, we show that angiogenic activation induces differentiation of macrophages from bone marrow-derived as well as from bone marrow-independent VW-SCs. The latter ones are at least partially yolk sac-independent, too. Those VW-SC-derived macrophages critically contribute to angiogenesis, making them an attractive target to interfere with pathological angiogenesis in cancer and atherosclerosis as well as with regenerative angiogenesis in ischemic cardiovascular disorders.
KW  - macrophages
KW  - angiogenesis
KW  - bone marrow-derived monocytes
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299724
VL  - 13
IS  - 3
ER  -