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Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells

Yeela Talmor1, Eliezer Golan, Sydney Benchetrit

  • 1Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, Kfar-Saba, Tchernichovsky 59, Kfar-Saba 44281, Israel.

American Journal of Physiology. Renal Physiology
|March 21, 2008
PubMed

Insights

Calcitriol may protect blood vessels by counteracting the harmful effects of advanced glycation end products (AGEs) on endothelial cells. This vitamin D analog reduces AGEs-induced inflammation and improves nitric oxide synthase function.

Area of Science:

  • Vascular biology
  • Endocrinology
  • Molecular medicine

Background:

  • Advanced glycation end products (AGEs) are implicated in vascular dysfunction, particularly in diabetes and uremia.
  • Calcitriol, a form of Vitamin D, is known to potentially improve cardiovascular complications.

Purpose of the Study:

  • To investigate whether calcitriol can modify endothelial cell responses to AGEs stimulation.
  • To examine the effects of AGEs and calcitriol on the nuclear factor-kappaB (NF-κB) pathway in endothelial cells.

Main Methods:

  • Endothelial cells were treated with AGE-human serum albumin (HSA) with or without calcitriol.
  • Assessed endothelial nitric oxide synthase (eNOS) mRNA expression and activity.
  • Measured AGEs receptor, interleukin-6 (IL-6) mRNA, and NF-κB pathway components (NF-κB-p65, IκBα, p-IκBα).

Main Results:

  • AGE-HSA decreased eNOS expression and activity, which was improved by calcitriol.
  • Calcitriol blunted AGE-HSA-induced increases in AGEs receptor and IL-6 mRNA.
  • AGE-HSA enhanced NF-κB-p65 DNA binding activity; calcitriol reversed this by increasing IκBα expression and decreasing p-IκBα.

Conclusions:

  • Calcitriol demonstrates vascular protective effects against AGEs-induced endothelial dysfunction.
  • Calcitriol mitigates AGEs-mediated inflammation and preserves eNOS system function.
  • These findings suggest calcitriol's potential therapeutic role in conditions associated with elevated AGEs.

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