E2F5 Promotes Vascular Endothelial Cell Proliferation and Angiogenesis in Diabetic Lower Limb Ischemia via an Autophagy-Related Mechanism
Abstract
BACKGROUND: Because vascular regeneration of diabetic lower limb ischemia (LLI) and prevention of disease progression is a major problem, we explored the molecular mechanism of E2F transcription factor 5 (E2F5) in regulating autophagy to promote angiogenesis in diabetic HLI. METHODS AND RESULTS: The streptozotocin-induced diabetic mice model, hindlimb ischemia (HLI) model and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were constructed for in vivo and in vitro assays. Autophagy inhibitor, 3-methyladenine, reversed the effects of E2F5 overexpression on microtubule-associated protein 1 light chain 3B (LC3B) expression, cell proliferation, migration and tube formation, supporting the involvement of autophagy in E2F5-mediated HUVEC restoration. In vivo injection of E2F5 overexpressed lentivirus also promoted angiogenesis in diabetic HLI mice, concomitant with autophagy activation. Phosphorylated yes-associated protein (pYAP) expression in HUVECs was upregulated after HG treatment and E2F5 overexpression reversed this change. pYAP colocalized with CD31, and pYAP expression was decreased after E2F5 overexpression. Treatment with Ki16425 increased pYAP expression and affected the influence of E2F5 on the proliferation, migration and tubule formation of HUVECs, and LC3B expression. CONCLUSIONS: E2F5 promoted angiogenesis by downregulating pYAP, which is associated with autophagy activation. These findings provide a novel therapeutic strategy for diabetic LLI.
Related
- A collagen Vα1-derived fragment inhibits FGF-2 induced-angiogenesis by modulating endothelial cells plasticity through its heparin-binding site
- Macrophage‐Derived Glycoprotein Nonmetastatic Melanoma Protein B Attenuates Cardiac Dysfunction by Promoting Vascular Endothelial Growth Factor‐Independent Angiogenesis
- Eriocitrin promotes apoptosis and inhibits invasion and proliferation of androgen-independent prostate cancer via the PI3K/AKT/mTOR pathway
- Circular RNA circ_0006523 promotes lipid accumulation and proliferation of diffuse large B-cell lymphoma via the miR-659-3p/SPHK1 axis
- Coupling of cell proliferation to the segmentation clock promotes robust somite scaling
BibTeX
@article{zhan2026e2f5,
title = {{E2F5 Promotes Vascular Endothelial Cell Proliferation and Angiogenesis in Diabetic Lower Limb Ischemia via an Autophagy-Related Mechanism}},
author = {Yuyan Zhan and Hongwei Shi and Xiaoying Miu and Xiaoping Peng and Jungang Nie and Dong Liu and Qiong Duan and Ting Kang},
journal = {Circulation Journal},
year = {2026},
month = sep,
doi = {10.1253/circj.cj-25-0736},
url = {https://www.jstage.jst.go.jp/article/circj/90/10/90_CJ-25-0736/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - E2F5 Promotes Vascular Endothelial Cell Proliferation and Angiogenesis in Diabetic Lower Limb Ischemia via an Autophagy-Related Mechanism
AU - Yuyan Zhan
AU - Hongwei Shi
AU - Xiaoying Miu
AU - Xiaoping Peng
AU - Jungang Nie
AU - Dong Liu
AU - Qiong Duan
AU - Ting Kang
PY - 2026
DA - 2026/09/25
JO - Circulation Journal
DO - 10.1253/circj.cj-25-0736
UR - https://www.jstage.jst.go.jp/article/circj/90/10/90_CJ-25-0736/_article
AB - BACKGROUND: Because vascular regeneration of diabetic lower limb ischemia (LLI) and prevention of disease progression is a major problem, we explored the molecular mechanism of E2F transcription factor 5 (E2F5) in regulating autophagy to promote angiogenesis in diabetic HLI. METHODS AND RESULTS: The streptozotocin-induced diabetic mice model, hindlimb ischemia (HLI) model and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were constructed for in vivo and in vitro assays. Autophagy inhibitor, 3-methyladenine, reversed the effects of E2F5 overexpression on microtubule-associated protein 1 light chain 3B (LC3B) expression, cell proliferation, migration and tube formation, supporting the involvement of autophagy in E2F5-mediated HUVEC restoration. In vivo injection of E2F5 overexpressed lentivirus also promoted angiogenesis in diabetic HLI mice, concomitant with autophagy activation. Phosphorylated yes-associated protein (pYAP) expression in HUVECs was upregulated after HG treatment and E2F5 overexpression reversed this change. pYAP colocalized with CD31, and pYAP expression was decreased after E2F5 overexpression. Treatment with Ki16425 increased pYAP expression and affected the influence of E2F5 on the proliferation, migration and tubule formation of HUVECs, and LC3B expression. CONCLUSIONS: E2F5 promoted angiogenesis by downregulating pYAP, which is associated with autophagy activation. These findings provide a novel therapeutic strategy for diabetic LLI.
SN - 1347-4820
SN - 1346-9843
ER -