Angiogenesis
Fig. 1: EM picture of mitochondria in endothelial cells. Scale 1 µm.
These research projects deal with the analysis of physiological and pathological angiogenesis (= new blood vessel formation), e.g. in tumors or in proliferative retinopathy. We are particularly interested in molecular processes in the endothelium and the influence of inflammatory cells on the modulation of blood vessels formation.
Fig. 2: Mouse aortic ring stained for Isolectin GS-IB4 to visualize the angiogenic sprouts.
In addition to the standard molecular biological methods, the angiogenic mechanisms are examined using the following models:
-
in vitro: e.g.: isolation and culture of primary cells from the mouse (microglia, macrophages and endothelial cells; Fig. 1); Co-cultures, endothelial cell sprouting experiments
- ex-vivo: aortic ring and coroid sprouting angiogenesis experiments (Fig. 2)
Fig. 3: Mouse retina at postnatal day 6 stained with Isolectin GS-IB4 to visualize the retinal vessels.
- in vivo: physiological angiogenesis in the mouse retina (Fig. 3), murine oxygen-induced retinopathy model (OIR model, Fig. 4) and syngeneic tumors in mice
Fig. 4: PAS-stained retinal cross section of the mouse with pathological vessels.
If you are interested in working in one of our projects, please contact us:
Selected Publications:
- Klotzsche-von Ameln A, Sprott D. Harnessing retinal phagocytes to combat pathological neovascularization in ischemic retinopathies? Pflugers Arch. 2022 Jun;474(6):575-590.
- Korovina I, Neuwirth A, Sprott D, Troullinaki M, Poitz DM, Deussen A, Klotzsche-von Ameln A. Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment. J Innate Immun. 2019 Oct 1:1-9.
- Sprott D, Poitz DM, Korovina I, Ziogas A, Phieler J, Chatzigeorgiou A, Mitroulis I, Deussen A, Chavakis T, Klotzsche-von Ameln A. Endothelial-Specific Deficiency of ATG5 (Autophagy Protein 5) Attenuates Ischemia-Related Angiogenesis. Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1137-1148.
- Troullinaki M, Alexaki VI, Mitroulis I, Witt A, Klotzsche-von Ameln A, Chung KJ, Chavakis T, Economopoulou M. Nerve growth factor regulates endothelial cell survival and pathological retinal angiogenesis. J Cell Mol Med. 2019 Apr;23(4):2362-2371.
- Troullinaki M, Garcia-Martin R, Sprott D, Klotzsche-von Ameln A, Grossklaus S, Mitroulis I, Chavakis T, Economopoulou M. 53BP1 Deficiency Promotes Pathological Neovascularization in Proliferative Retinopathy. Thromb Haemost. 2019 Mar;119(3):439-448.
- Korovina I, Neuwirth A, Sprott D, Weber S, Sardar Pasha SPB, Gercken B, Breier G, El-Armouche A, Deussen A, Karl MO, Wielockx B, Chavakis T, Klotzsche-von Ameln A. Hematopoietic hypoxia-inducible factor 2α deficiency ameliorates pathological retinal neovascularization via modulation of endothelial cell apoptosis. FASEB J. 2019 Feb;33(2):1758-1770.
- Klotzsche - von Ameln A, Cremer S, Hoffmann J, Schuster P, Khedr S, Korovina I, Troulinaki M, Neuwirth A, Sprott D, Chatzigeorgiou A, Economopoulou M, Orlandi A, Hain A, Zeiher AM, Deussen A, Hajishengallis G, Dimmeler S, Chavakis T, Emmanouil Chavakis. Endogenous developmental endothelial locus-1 limits ischemia-related angiogenesis by blocking inflammation. Thromb Haemost. 2017 Jun 2;117(6):1150-1163.
- Economopoulou M, Avramovic N, Klotzsche-von Ameln A, Korovina I, Sprott D, Samus M, Gercken B, Troullinaki M, Grossklaus S, Funk RH, Li X, Imhof BA, Orlova VV, Chavakis T. Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel normalisation in proliferative retinopathy. Thromb Haemost. 2015 Nov 25;114(6):1241-9.
- Klotzsche-von Ameln A, Prade I, Grosser M, Kettelhake A, Rezaei M, Chavakis T, Flamme I, Wielockx B, Breier G. PHD4 stimulates tumor angiogenesis in osteosarcoma cells via TGF-α. Mol Cancer Res. 2013 Nov;11(11):1337-48.
- Zhang F, Li Y, Tang Z, Kumar A, Lee C, Zhang L, Zhu C, Klotzsche-von Ameln A, Wang B, Gao Z, Zhang S, Langer HF, Hou X, Jensen L, Ma W, Wong W, Chavakis T, Liu Y, Cao Y, Li X. Proliferative and survival effects of PUMA promote angiogenesis. Cell Rep. 2012 Nov 29;2(5):1272-85.
- Klotzsche-von Ameln A, Muschter A, Mamlouk S, Kalucka J, Prade I, Franke K, Rezaei M, Poitz DM, Breier G, Wielockx B. Inhibition of HIF prolyl hydroxylase-2 blocks tumor growth in mice through the antiproliferative activity of TGFβ. Cancer Res. 2011 May 1;71(9):3306-16.