biostudies-literatureOliveira RHMNHLBI NIH HHSNCI NIH HHSNational Institutes of Health1351753https://www.ebi.ac.uk/biostudies/studies/S-EPMC10917925biostudies-literatureUnknown15<b>Introduction:</b> Several signaling pathways are activated during hypoxia to promote angiogenesis, leading to endothelial cell patterning, interaction, and downstream signaling. Understanding the mechanistic signaling differences between endothelial cells under normoxia and hypoxia and their response to different stimuli can guide therapies to modulate angiogenesis. We present a novel mechanistic model of interacting endothelial cells, including the main pathways involved in angiogenesis. <b>Methods:</b> We calibrate and fit the model parameters based on well-established modeling techniques that include structural and practical parameter identifiability, uncertainty quantification, and global sensitivity. <b>Results:</b> Our results indicate that the main pathways involved in patterningFrontiers in physiologyEndothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.PMC10917925R01HL101200 R01CA138264 R01HL-141325R01 CA138264R01 HL141325R01 HL101200Annex BHOliveira RHMPopel ASfalseEndothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.<b>Introduction:</b> Several signaling pathways are activated during hypoxia to promote angiogenesis, leading to endothelial cell patterning, interaction, and downstream signaling. Understanding the mechanistic signaling differences between endothelial cells under normoxia and hypoxia and their response to different stimuli can guide therapies to modulate angiogenesis. We present a novel mechanistic model of interacting endothelial cells, including the main pathways involved in angiogenesis. <b>Methods:</b> We calibrate and fit the model parameters based on well-established modeling techniques that include structural and practical parameter identifiability, uncertainty quantification, and global sensitivity. <b>Results:</b> Our results indicate that the main pathways involved in patterning2024-01-01T00:00:00Z20242025-04-18T15:27:05.602Z2025-04-07T02:07:12.175ZS-EPMC109179253845584410.3389/fphys.2024.1351753