Vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness

  • P. A
  • M. C
  • P. F
 et al. 
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Objective: Experimental evidence indicates that circulating insulin-like growth factor-1 (IGF-1) counteracts vascular aging and atherosclerosis, for which increased carotid artery intima-media thickness (IMT) is a marker. Yet, IGF-1 concentrations have been inconsistently associated with carotid IMT in epidemiological studies. Since vitamin D is also implicated in vascular protection and affects IGF-1 biology, we hypothesized that it would influence the effect of IGF-1 on IMT. Methods: The relationship between carotid IMT and fasting serum IGF-1 was examined across strata of 25-hydroxyvitamin D [25(OH)D] in 472 participants in the Baltimore Longitudinal Study of Aging (BLSA) with well-controlled blood pressure and in 165 treatment-naive patients with essential hypertension from the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) study. Moreover, the interplay between vitamin D and IGF-1 was preliminarily explored in EA.hy926 endothelial cells. Results: After adjusting for age, sex, BMI, renal function, smoking, systolic blood pressure, LDL-cholesterol, glycemia, antihypertensive or lipid-lowering therapy, season, parathyroid hormone, and vitamin D supplementation, IGF-1 was significantly and negatively associated with carotid IMT only within the lowest 25(OH)D quartile (range 6.8-26 ng/mL) of the BLSA (. β -0.095, p = 0.03). Similarly, a significant negative correlation between IGF-1 and carotid IMT was found after full adjustment only in MAGIC patients with 25(OH)D concentrations below either the deficiency cut-off of 20 ng/mL (. β -0.214, p = 0.02) or 26 ng/mL (. β -0.174, p = 0.03). Vitamin D dose-dependently decreased hydrogen peroxide-induced endothelial cell oxidative stress and apoptosis, which were further inhibited by IGF in the presence of low, but not high vitamin D concentration. Conclusions: Circulating IGF-1 is vasoprotective primarily when vitamin D levels are low. Future studies should address the mechanisms of vitamin D/IGF-1 interaction.

Author-supplied keywords

  • age distribution
  • aged
  • antihypertensive agent
  • antilipemic agent
  • apoptosis
  • arterial wall thickness
  • article
  • blood pressure regulation
  • body mass
  • controlled study
  • endothelium cell
  • essential hypertension
  • female
  • glucose blood level
  • human
  • human cell
  • hypothesis
  • kidney function
  • longitudinal study
  • low density lipoprotein cholesterol
  • major clinical study
  • male
  • microalbuminuria
  • oxidative stress
  • parathyroid hormone
  • season
  • sex difference
  • smoking
  • somatomedin C
  • systolic blood pressure
  • vitamin D
  • vitamin supplementation

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  • Ameri P.

  • Canepa M.

  • Fabbi P.

  • Leoncini G.

  • Milaneschi Y.

  • Mussap M.

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