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Positive versus negative effects of VEGF165 on Ca2+ signaling and NO production in human endothelial cells.
- Source :
-
American Journal of Physiology: Heart & Circulatory Physiology . Jan2017, Vol. 312 Issue 1, pH173-H181. 9p. - Publication Year :
- 2017
-
Abstract
- The role increased vascular endothelial growth factor (VEGF) plays in vascular function during normal vs. preeclamptic pregnancy has been a source of some controversy of late. In this study, we seek to understand how VEGF165 influences vasodilator production via Ca2+ signaling mechanisms in human endothelial cells. We utilize human umbilical vein endothelial cells (HUVEC) as well as intact ex vivo human umbilical vein (HUV Endo) to address direct stimulation of Ca2+ and NO by VEGF165 alone, as well as the effect of VEGF165 on subsequent ATP-stimulated Ca2+ signaling and NO production. We show that VEGF165 stimulates Ca2+ responses in both HUVEC and HUV Endo, which results in a corresponding increase in NO production in HUV Endo. Longerterm VEGF165 pretreatment then inhibits sustained Ca2+ burst responses to ATP in HUVEC and HUV Endo. This is paralleled by a corresponding drop in ATP-stimulated NO production in HUV Endo, likely through inhibition of Cx43 gap-junction function. Thus, although VEGF165 makes a small initial positive impact on vasodilator production via direct stimulation of Ca2+ responses, this is outweighed by the greater subsequent negative impact on Ca2+ bursts and vasodilator production promoted by more potent agonists such as ATP. Overall, elevated levels of VEGF165 associated with preeclampsia could contribute to the endothelial dysfunction by preventing Ca2+ bursts to other agonists including but not limited to ATP. [ABSTRACT FROM AUTHOR]
- Subjects :
- *VASCULAR endothelial growth factors
*ENDOTHELIAL cells
Subjects
Details
- Language :
- English
- ISSN :
- 03636135
- Volume :
- 312
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Heart & Circulatory Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 132985382
- Full Text :
- https://doi.org/10.1152/ajpheart.00924.2015