Plasminogen activator inhibitor-1 inhibits angiogenic signaling by uncoupling vascular endothelial growth factor receptor-2-αVβ3 integrin cross talk.

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Abstract

Plasminogen activator inhibitor-1 (PAI-1) regulates angiogenesis via effects on extracellular matrix proteolysis and cell adhesion. However, no previous study has implicated PAI-1 in controlling vascular endothelial growth factor (VEGF) signaling. We tested the hypothesis that PAI-1 downregulates VEGF receptor-2 (VEGFR-2) activation by inhibiting a vitronectin-dependent cooperative binding interaction between VEGFR-2 and αVβ3.

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Journal ID (iso-abbrev): Arterioscler. Thromb. Vasc. Biol.

Title: Arteriosclerosis, thrombosis, and vascular biology

ISSN (Electronic): 1524-4636

ISSN (Print): 1079-5642

Publication date (Electronic): Jan 2015

Volume: 35

Issue: 1

Affiliations

[1 ] From the Departments of Internal Medicine and Medical Pharmacology and Physiology (J.W., T.L.S., M.L., W.P.F.), the Research Service, Harry S. Truman Memorial Veterans Hospital (W.P.F.), University of Missouri School of Medicine, Columbia; the Drug Discovery Research Center, Luzhou Medical College, Luzhou, Sichuan, China (J.W., M.L., L.W., R.L., M.R., J.X., Z.Z., W.M., T.L.); and the Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (D.A.L.). wuji@missouri.edu.

[2 ] From the Departments of Internal Medicine and Medical Pharmacology and Physiology (J.W., T.L.S., M.L., W.P.F.), the Research Service, Harry S. Truman Memorial Veterans Hospital (W.P.F.), University of Missouri School of Medicine, Columbia; the Drug Discovery Research Center, Luzhou Medical College, Luzhou, Sichuan, China (J.W., M.L., L.W., R.L., M.R., J.X., Z.Z., W.M., T.L.); and the Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (D.A.L.).

Article

Publisher Item ID: ATVBAHA.114.304554 Mid ID: NIHMS638860

DOI: 10.1161/ATVBAHA.114.304554

PMC ID: 4270947

PubMed ID: 25378411

SO-VID: 607b932b-4bc9-471c-a88a-a3d1e9d49a54

History

Keywords: plasminogen activator inhibitor-1,vascular endothelial growth factor A,very low-density lipoprotein receptor,vitronectin

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Keywords: plasminogen activator inhibitor-1, vascular endothelial growth factor A, very low-density lipoprotein receptor, vitronectin

Plasminogen activator inhibitor-1 inhibits angiogenic signaling by uncoupling vascular endothelial growth factor receptor-2-αVβ3 integrin cross talk.

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