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Elevated fibroblast growth factor‐2 increases tumor necrosis factor‐α induced endothelial cell death in high glucose
Author(s) -
Clyne Alisa Morss,
Zhu Han,
Edelman Elazer R.
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21476
Subject(s) - propidium iodide , programmed cell death , fibroblast growth factor , endothelial stem cell , apoptosis , tumor necrosis factor alpha , biology , cell cycle , vascular endothelial growth inhibitor , endocrinology , microbiology and biotechnology , medicine , vascular endothelial growth factor a , vascular endothelial growth factor , cancer research , biochemistry , receptor , in vitro , vegf receptors
Glucose and tumor necrosis factor‐α (TNFα) concentrations are elevated in diabetes. Both of these factors correlate with diabetic vasculopathy and endothelial cell apoptosis, yet their combined effects have not been measured. We have previously shown that the angiogenic growth factor fibroblast growth factor‐2 (FGF‐2), which is generally protective against endothelial cell death, is similarly elevated in high glucose conditions. We therefore investigated the effect of TNFα on endothelial cell death under normal and elevated glucose conditions, with a particular focus on FGF‐2. Porcine aortic endothelial cells were cultured in 5 and 30 mM glucose and stimulated with TNFα, together with FGF‐2 or a neutralizing FGF‐2 antibody. Cell death was measured via cell counts or an annexin apoptotic assay, and cell cycle phase was determined by propidium iodide labeling. TNFα‐induced endothelial cell death increased for cells in high glucose, and cell death was enhanced with increasing FGF‐2 exposure and negated by a neutralizing FGF‐2 antibody. Endothelial cells were most susceptible to TNFα‐induced cell death when stimulated with FGF‐2 18 h prior to TNFα, corresponding to cell entry into S phase of the proliferative cycle. The FGF‐2 associated increase in TNFα‐induced cell death was negated by blocking cell entry into S phase. Endothelial cell release of FGF‐2 in high glucose leads to cell cycle progression, which makes cells more susceptible to TNFα‐induced cell death. These data suggest that growth factor outcomes in high glucose depend on secondary mediators such as cytokines and stimulation cell cycle timing. J. Cell. Physiol. 217: 86–92, 2008. © 2008 Wiley‐Liss, Inc.