TY - JOUR
T1 - Vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness
AU - Ameri, P.
AU - Canepa, M.
AU - Fabbi, P.
AU - Leoncini, G.
AU - Milaneschi, Y.
AU - Mussap, M.
AU - AlGhatrif, M.
AU - Balbi, M.
AU - Viazzi, F.
AU - Murialdo, G.
AU - Pontremoli, R.
AU - Brunelli, C.
AU - Ferrucci, L.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1016/j.atherosclerosis.2014.08.022
DO - 10.1016/j.atherosclerosis.2014.08.022
M3 - Article
SN - 0021-9150
VL - 236
SP - 418
EP - 425
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -
