Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways.
Parathyroid hormone (PTH), the major systemic calcium-regulating hormone, has been linked to uremic vascular changes. Considering the possible deleterious action of PTH on vascular structures, it seemed logical to evaluate the impact of PTH on the receptor of advanced glycation end products (RAGE) and interleukin 6 (IL-6) mRNA and protein expression, taking into account that such parameters might be involved in the pathogenesis of vascular calcification, atherosclerosis, and/or arteriolosclerosis. Human umbilical vein cord endothelial cells (HUVEC) were stimulated for 24 h with 10(-12)-10(-10) mol/l PTH. The mRNA expression of RAGE and IL-6 was established by reverse transcriptase/PCR techniques. RAGE protein levels were determined by Western blot and IL-6 secretion was measured by ELISA. The pathways by which PTH may have an effect on HUVEC functions were evaluated. PTH (10(-11)-10(-10)mol/l) significantly increased RAGE mRNA and protein expression. PTH also significantly increased IL-6 mRNA expression without changes at protein levels. The addition of protein kinase (PKC or PKA) inhibitors or nitric oxide (NO) synthase inhibitors significantly reduced the RAGE and IL-6 mRNA expression and the RAGE protein expression. PTH stimulates the mRNA expressions of RAGE and IL-6 and the protein expression of RAGE. These stimulatory effects are probably through PKC and PKA pathways and are also NO dependent. Such data may explain the possible impact of PTH on the atherosclerotic and arteriosclerotic progression.
Rashid
Gloria
G
Dept. of Nephrology and Hypertension, Meir Medical Center, Tchernichovsky 59, Kfar-Saba 44281, Israel. Gloriar@clalit.org.il
Bernheim
Jacques
J
Green
Janice
J
Benchetrit
Sydney
S
D050197:Atherosclerosis / Q000209:etiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000096:biosynthesis / Q000502:physiology*; D011247:Pregnancy; D011494:Protein Kinases / Q000502:physiology*; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D013873:Thionucleotides / Q000494:pharmacology
D015850:Interleukin-6; D009281:Naphthalenes; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D011494:Protein Kinases; C058819:calphostin C; D019331:NG-Nitroarginine Methyl Ester