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

Abstract：

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.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Ameri P,Canepa M,Fabbi P,Leoncini G,Milaneschi Y,Mussap M,AlGhatrif M,Balbi M,Viazzi F,Murialdo G,Pontremoli R,Brunelli C,Ferrucci L

doi

10.1016/j.atherosclerosis.2014.08.022

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

418-25

issue

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(14)01349-5

journal_volume

236

pub_type

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