Angiogenic behavior of human umbilical vein endothelial cells in hydrogel containing lyophilized powder of decellularized adipose tissue from high-fat diet-fed or exercise-trained rats

Background Obesity often leads to impaired angiogenesis through extracellular matrix (ECM) reorganization, whereas exercise training has beneficial effects on ECM remodeling and capillary density in adipose tissues. However, the relationship between angiogenesis and ECM changes due to high-fat diet (HFD) intake and exercise training remains unclear.Purpose To evaluate in vitro tube-like formation of human umbilical vein endothelial cells (HUVECs) using a three-dimensional hydrogel containing decellularized adipose tissue (DAT) powder derived from the adipose tissues of HFD-fed or exercise-trained (EX) rats.Methods DAT was prepared from the inguinal and epididymal adipose tissues of rats in four intervention groups: normal diet (ND)-fed sedentary, HFD-fed sedentary, ND-fed EX, or HFD-fed EX groups. DAT was incorporated into a three-dimensional hydrogel, and proteomic analysis of DAT was performed. Tube-like network formation was evaluated in HUVECs cultured in DAT hydrogel.Results Several angiogenic marker proteins were identified using immunoblotting. Inguinal DAT hydrogel from the HFD-EX group exhibited greater development of network connectivity, branching, and length of HUVECs compared to the other groups. Similar phenomena were observed in epididymal DAT hydrogels from the HFD groups compared to those from the ND groups. HUVEC tube-like network formation was greater in the epididymal than in the inguinal hydrogels, with enhanced protein expression of vascular endothelial growth factor receptor 2, focal adhesion kinase, and vascular endothelial cadherin. Exploratory proteomic analysis implied fat depot- and intervention-dependent differences in DAT composition.Conclusion HUVEC angiogenic behavior may be sensitive to HFD- and exercise training-associated changes in DAT composition in a fat depot-dependent manner.