Mouse Proepicardium Exhibits a Sprouting Response to Exogenous Proangiogenic Growth Factors in vitro.
Angiogenesis contributes to the generation of the vascular bed but also affects the progression of many diseases, such as tumor growth. Many details of the molecular pathways controlling angiogenesis are still undefined due to the lack of appropriate models. We propose the proepicardial explant as a suitable model for studying certain aspects of angiogenesis. The proepicardium (PE) is a transient embryonic structure that contains a population of undifferentiated endothelial cells (ECs) forming a vascular net continuous with the sinus venosus. In this paper, we show that PE explants give rise to CD31-positive vascular sprouts in the presence of basic fibroblast growth factor (bFGF) and 2 isoforms of vascular endothelial growth factor A (VEGF-A), i.e. VEGF-A120 and VEGF-A164. Vascular sprouts exhibit differences in number, length, thickness and the number of branches, depending on the combination of growth factors used. Moreover, the ECs of the sprouts express various levels of mRNA for Notch1 and its ligand Dll4. Additionally, stimulation with bFGF/VEGF-A164 upregulates the expression of Lyve-1 antigen in the ECs in the sprouts. In summary, we present a new model for angiogenesis studies involving mouse PE as a source of ECs. We believe that our model may act as a supplementary assay for angiogenesis studies along with the existing models.
Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
Justyna
J
Niderla-Bielińska
Bogdan
B
Ciszek
Ewa
E
Jankowska-Steifer
Aleksandra
A
Flaht-Zabost
Grzegorz
G
Gula
Dorota M
DM
Radomska-Leśniewska
Anna
A
Ratajska
D048868:Adaptor Proteins, Signal Transducing; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006023:Glycoproteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010496:Pericardium / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism; D036224:Receptor, EphB4 / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016222:Fibroblast Growth Factor 2; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D036183:Receptor, EphB2; D036224:Receptor, EphB4; D051881:Receptor, Notch1; D042461:Vascular Endothelial Growth Factor A; C519665:DLL4 protein, mouse; C497762:Notch1 protein, mouse; C492273:LYVE1 protein, mouse; C586311:Ephb2 protein, mouse; C086681:Ephb4 protein, mouse