TY - JOUR
T1 - Vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness
AU - Ameri, Pietro
AU - Canepa, Marco
AU - Fabbi, Patrizia
AU - Leoncini, Giovanna
AU - Milaneschi, Yuri
AU - Mussap, Michele
AU - AlGhatrif, Majd
AU - Balbi, Manrico
AU - Viazzi, Francesca
AU - Murialdo, Giovanni
AU - Pontremoli, Roberto
AU - Brunelli, Claudio
AU - Ferrucci, Luigi
N1 - Funding Information:
This study was supported by the Intramural Research Program of the National Institute on Aging (BLSA) and by the Progetto di Ricerca d'Ateneo 2011 research grant funded by the University of Genova, Italy (MAGIC) .
Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2014/8/12
Y1 - 2014/8/12
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.
KW - Aging
KW - Atherosclerosis
KW - Endothelial
KW - IGF-1
KW - Intima-media thickness
KW - Vitamin D
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U2 - 10.1016/j.atherosclerosis.2014.08.022
DO - 10.1016/j.atherosclerosis.2014.08.022
M3 - Article
C2 - 25150940
AN - SCOPUS:84907068484
VL - 236
SP - 418
EP - 425
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 2
ER -