Vascular Endothelial Growth Factor–Induced Endothelial Cell Migration and Proliferation Depend on a Nitric Oxide–Mediated Decrease in Protein Kinase Cδ Activity
- 6 August 1999
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 85 (3) , 247-256
- https://doi.org/10.1161/01.res.85.3.247
Abstract
—Vascular endothelial growth factor (VEGF) promotes angiogenesis and endothelial cell (EC) migration and proliferation by affecting intracellular mediators, only some of which are known, distal to its receptors. Protein kinase C (PKC) participates in the function of VEGF, but the role of individual PKC isoenzymes is unknown. In this study, we tested the importance of the activity of specific PKC isoenzymes in human EC migration and proliferation in response to VEGF. PKCδ specific activity was depressed by the addition of VEGF (by 41±8% [P<0.05] at 24 hours) in human umbilical vein ECs (HUVECs) and in a HUVEC-derived EC line, ECV, without changing the total amount of either protein or mRNA encoding PKCδ. Neither basic fibroblast growth factor (FGF-2) nor serum altered PKCδ specific activity. The VEGF-induced decrease of PKCδ activity, which began at 8 hours after stimulation, was strongly blocked by pretreatment with the nitric oxide (NO) synthase inhibitor NG-monomethyl-l-arginine in HUVECs; NO re...Keywords
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