Attribution 4.0 International (CC BY 4.0)2023-09-142023-09-142023-09-09Al-Ghadban, S., Walczak, S. G., Isern, S. U., Martin, E. C., Herbst, K. L., & Bunnell, B. A. (2023). Enhanced Angiogenesis in HUVECs Preconditioned with Media from Adipocytes Differentiated from Lipedema Adipose Stem Cells In Vitro. International journal of molecular sciences, 24(17), 13572. https://doi.org/10.3390/ijms2417135721422-0067https://hdl.handle.net/20.500.12503/32409Lipedema is a connective tissue disorder characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. This project aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). The impacts on the expression levels of multiple endothelial and angiogenic markers [CD31, von Willebrand Factor (vWF), angiopoietin 2 (ANG2), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMPs), NOTCH and its ligands] in HUVECs were investigated. The data demonstrate an increased expression of CD31 and ANG2 at both the gene and protein levels in HUVECs treated with AQL CM in 2D monolayer and 3D cultures compared to untreated cells. Furthermore, the expression of the vWF, NOTCH 4, and DELTA-4 genes decreased. In contrast, increased VEGF, MMP9, and HGF gene expression was detected in HUVECs treated with AQL CM cultured in a 2D monolayer. In addition, the results of a tube formation assay indicate that the number of formed tubes increased in lipedema-treated HUVECs cultured in a 2D monolayer. Together, the data indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.http://creativecommons.org/licenses/by/4.0/angiogenesisendothelial cellslipedemanotch signalingHumansVascular Endothelial Growth Factor A / geneticsHuman Umbilical Vein Endothelial Cellsvon Willebrand Factor / geneticsLipedemaAdipocytesCulture Media, Conditioned / pharmacologyStem CellsArticle© 2023 by the authors.2417