Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factor.
BACKGROUND
We showed previously that parathyroid hormone (PTH) may stimulate the endothelial expression of pro-atherosclerotic and pro-inflammatory markers. Considering the impact of PTH on vasculature, we decided to evaluate its effect on mRNA and intra-cellular protein expressions of endothelial vascular endothelial growth factor (VEGF) taking into account that VEGF may play a role in the pathogenesis of endothelial dysfunctions.


METHODS
Human umbilical vein cords endothelial cells (HUVEC) were stimulated for 24 h with 10(-12)-10(-10) mol L(-1) PTH. The VEGF-165 mRNA expression (critical in stimulating endothelial cell proliferation) was evaluated by RT/PCR and the intra-cellular VEGF protein expression by flow cytometry. The pathways by which PTH may have an effect on VEGF expression were also evaluated.


RESULTS
PTH (10(-10) mol L(-1)) significantly increased VEGF-165 mRNA expression (P < 0.05). The addition of 50 nmol L(-1) protein kinase C (PKC) and 10 micromol L(-1) protein kinase A (PKA) inhibitors significantly reduced the VEGF-165 mRNA expression (P = 0.01). We also examined whether nitric oxide (NO) may be involved in the PTH-induced stimulation of VEGF-165 expression. Pre-treatment of the cells with 200 micromol L-nitro arginine methyl ester (L-NAME, NO synthase inhibitor) was found to inhibit VEGF-165 mRNA expression (P = 0.006). VEGF protein could not be detected in the medium of HUVEC but it was present in the cell cytoplasm. PTH had no significant effect on cytoplasmatic VEGF protein expression.


CONCLUSIONS
The stimulatory effect of PTH on endothelial VEGF-165 mRNA expression is partly through PKC and PKA pathways and is also NO dependent.
Rashid
G
G
Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, Kfar-Saba, Israel.
Bernheim
J
J
Green
J
J
Benchetrit
S
S
D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010281:Parathyroid Hormone; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019331:NG-Nitroarginine Methyl Ester