Cited by 649Angiogenesis and VEGF in CancerVascular Tumors and AngiosarcomasCell death mechanisms and regulation

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Angiopoietin-1 Regulates Endothelial Cell Survival Through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction Pathway

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Kim, Injune, Kim, Hwan Gyu, So, June-No, Kim, Joo Heon, Kwak, Hee Jin, Koh, Gou Young·2000·Circulation Research

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Abstract

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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Authors: Kim, I., Kim, H. G., So, J.-N., Kim, J. H., Kwak, H. J., & Koh, G. Y.
Affiliations: Woosuk University (KR)
ORCID: Kim, Injune
So, June-No
Koh, Gou Young
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2000-01-07
Volume: 86
Issue: 1
Pages: 24-29
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/01.res.86.1.24
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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Angiopoietin-1 Regulates Endothelial Cell Survival Through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction Pathway

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