The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Angiopoietin-1 Regulates Endothelial Cell Survival Through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction Pathway
Open accessAbstract
Abstract —Angiopoietin-1 (Ang1) is a strong apoptosis survival factor for endothelial cells. In this study, the receptor/second messenger signal transduction pathway for the antiapoptotic effect of Ang1 on human umbilical vein endothelial cells was examined. Pretreatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang1-induced antiapoptotic effect. Ang1 induced phosphorylation of Tie2 and the p85 subunit of phosphatidylinositol 3′-kinase (PI 3′-kinase) and increased PI 3′-kinase activity in a dose-dependent manner. The PI 3′-kinase–specific inhibitors wortmannin and LY294002 blocked the Ang1-induced antiapoptotic effect. Ang1 induced phosphorylation of the serine-threonine kinase Akt at Ser473 in a PI 3′-kinase–dependent manner. Expression of a dominant-negative form of Akt reversed the Ang1-induced antiapoptotic effect. Ang1 mRNA and protein were present in vascular smooth muscle cells but not in endothelial cells. Cultured vascular smooth muscle cells, but not human umbilical vein endothelial cells, secreted Ang1. These findings indicate that the Tie2 receptor, PI 3′-kinase, and Akt are crucial elements in the signal transduction pathway leading to endothelial cell survival induced by the paracrine activity of Ang1.
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“muscle secretes vascular endothelial growth factor (VEGF)45,46, angiopoietin 1 (REF.47) and IL-8 (REF.48) to regulate tissue angiogenesis, modulate blood flow and increase nutrient availability to support tissue growth27,49–52”
From Exerkines in health, resilience and disease (2022) · cites this paper as [47]
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Metadata
- Authors
- Kim, I., Kim, H. G., So, J.-N., Kim, J. H., Kwak, H. J., & Koh, G. Y.
- Affiliations
- Woosuk University (KR)
- Venue
- Circulation Research
- Published
- 2000-01-07
- Volume
- 86
- Issue
- 1
- Pages
- 24-29
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2167839699
- Cited by
- 649
- References
- 33
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 18 · 2023: 26 · 2022: 17 · 2021: 25 · 2020: 17 · 2019: 16 · 2018: 18 · 2017: 16 · 2016: 30 · 2015: 17 · 2014: 23 · 2013: 26 · 2012: 25
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre International de Recherche sur le Cancer
- Regeneron Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Vascular Tumors and Angiosarcomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- angiopoietin-1, endothelial cell survival, apoptosis, Tie2 receptor, phosphatidylinositol 3-kinase, Akt signaling, PI3K/Akt signaling, vascular smooth muscle cells, paracrine secretion, wortmannin, LY294002, dominant-negative Akt, human umbilical vein endothelial cells
- MeSH terms
- Cell Survival, Cells, Cultured, Endothelium, Vascular, Humans, Membrane Glycoproteins, Neoplasm Proteins, Peptide Fragments, Phosphorylation, Proto-Oncogene Proteins, Recombinant Proteins, Signal Transduction, Apoptosis, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Paracrine Communication, Angiopoietin-1, Receptor, TIE-2, Proto-Oncogene Proteins c-akt
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