Work

Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling

Year: 2021

Type: article

Abstract: OBJECTIVE: We aim to quantitatively characterize the crosstalk between VEGF- and FGF-mediated angiogenic signaling and endothelial sprouting, to gain mechanistic insights and identify novel therapeutic strategies. METHODS: We constructed an experimentally validated hybrid agent-based mathematical model that characterizes endothelial sprouting driven by FGF- and VEGF-mediated signaling. We predicted the total sprout length, number of sprouts, and average length by the mono- and co-stimulation of FGF and VEGF. RESULTS: The experimentally fitted and validated model predicts that FGF induces stronger angiogenic responses in the long-term compared with VEGF stimulation. Also, FGF plays a dominant role in the combination effects in endothelial sprouting. Moreover, the model suggests that ERK and Akt pathways and cellular responses contribute differently to the sprouting process. Last, the model predicts that the strategies to modulate endothelial sprouting are context-dependent, and our model can identify potential effective pro- and anti-angiogenic targets under different conditions and study their efficacy. CONCLUSIONS: The model provides detailed mechanistic insight into VEGF and FGF interactions in sprouting angiogenesis. More broadly, this model can be utilized to identify targets that influence angiogenic signaling leading to endothelial sprouting and to study the effects of pro- and anti-angiogenic therapies.

Source: Microcirculation

DOI: 10.1111/micc.12744

Authors: Min Song, Stacey D. Finley

Institution: University of Southern California

Language: English

Topic: Angiogenesis and VEGF in Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,300