PUBLICATION
Semaphorin 3F is elevated in serum of heart failure patients and inhibits cardiac angiogenesis via the VEGF/Akt/eNOS pathway
- Authors
- Petrova, D., Weberbauer, M., Reichert, S., Scheid, S., Esser, J., Fink, K., Duerschmied, D., Moser, M., Helbing, T.
- ID
- ZDB-PUB-250718-9
- Date
- 2025
- Source
- Journal of molecular and cellular cardiology plus 13: 100470100470 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Heart failure, Microvascular rarefaction, Remodeling, Semaphorin 3F, VEGF, eNOS
- MeSH Terms
- none
- PubMed
- 40678174 Full text @ J Mol Cell Cardiol Plus
Citation
Petrova, D., Weberbauer, M., Reichert, S., Scheid, S., Esser, J., Fink, K., Duerschmied, D., Moser, M., Helbing, T. (2025) Semaphorin 3F is elevated in serum of heart failure patients and inhibits cardiac angiogenesis via the VEGF/Akt/eNOS pathway. Journal of molecular and cellular cardiology plus. 13:100470100470.
Abstract
Left ventricular (LV) remodeling in heart failure (HF) is associated with vascular rarefaction and impaired angiogenesis. The inhibition of vascular endothelial growth factor (VEGF)-mediated angiogenesis is a key feature in the pathophysiology of HF. Semaphorin (Sema) 3F is a known inhibitor of VEGF signaling, but its role in HF remains to be elucidated. Serum Sema3F levels were measured in HF patients (n = 70) by ELISA and were compared to those in patients with coronary artery disease (CAD, n = 26). Sema3F levels were significantly increased in HF patients. Sema3F RNA and protein expression were upregulated by hypoxia in cardiac endothelial cells (HCECs) as demonstrated by quantitative RT-PCR and Western blotting (WB). In Matrigel® sprouting assays, endothelial cell sprouting and branching were decreased in response to HF patient serum, suggesting that HF serum contains anti-angiogenic factors. Recombinant human Sema3F attenuated VEGF-mediated angiogenesis in Matrigel® sprouting, spheroid sprouting and aortic ring assays. Vice versa, siRNA-based Sema3F knockdown promoted angiogenesis. In zebrafish, morpholino-based Sema3F knockdown led to increased mortality and induced a vascular phenotype. Mechanistically, Sema3F inhibited VEGF-induced Akt and eNOS phosphorylation in endothelial cells, and Sema3F knockdown increased phosphorylation of Akt and eNOS. Sema3F is elevated in serum of HF patients and has anti-angiogenic properties in cardiac angiogenesis through inhibition of the VEGF/Akt/eNOS pathway. Thus, targeting Sema3F could present a therapeutic approach to advanced HF in the future.
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