Enhanced Angiogenesis in HUVECs Preconditioned with Media from Adipocytes Differentiated from Lipedema Adipose Stem Cells In Vitro

Abstract

Lipedema 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.

Exploring the multifaceted role of obesity in breast cancer progression

“…The study demonstrated how co-culturing BCa cells with human adipocytes heightened the invasiveness of cancer cells through increased secretion of CCL5, suggesting that inhibiting CCL5 in the adipose microenvironment could be a promising strategy to curb highly malignant TNBC ( D’Esposito et al, 2016 ). Moreover, adipocytes have emerged as key players in vascular remodeling and angiogenesis, contributing significantly to the regulation of angiogenesis through the secretion of angiogenic cytokines like VEGF and angiopoietin ( Al-Ghadban et al, 2023 ).…”

The Expression of Adipogenic Marker Is Significantly Increased in Estrogen-Treated Lipedema Adipocytes Differentiated from Adipose Stem Cells In Vitro

“…Liposuction is the most effective treatment for decreasing fibrotic lipedema and fat, thereby improving mobility, which is essential for the quality of life of affected women [6][7][8]. While the etiology of lipedema remains unknown, hormones, genetic factors, inflammation, leaky dilated blood, and lymphatic vessels all contribute to the pathogenesis of lipedema [9][10][11][12][13][14].…”

“…However, ERβ KO mice have shown no change in body weight or fat distribution compared to wild-type mice [18,20]. Estrogen also regulates leptin and lipoprotein lipase genes (LPL) [21] and increases angiogenesis and vascular endothelial growth factor (VEGF) expression [22], a phenomenon observed in the SAT of lipedema patients [9,10,23]. The G protein-coupled estrogen receptor, GPER, has been implicated in regulating body weight, metabolism, inflammation, and pain [16,24,25].…”