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

被引:22
作者
Ameri, Pietro [1 ]
Canepa, Marco [1 ,2 ]
Fabbi, Patrizia [1 ]
Leoncini, Giovanna [1 ]
Milaneschi, Yuri [2 ,3 ,4 ]
Mussap, Michele [5 ]
AlGhatrif, Majd [6 ]
Balbi, Manrico [1 ]
Viazzi, Francesca [1 ]
Murialdo, Giovanni [1 ]
Pontremoli, Roberto [1 ]
Brunelli, Claudio [1 ]
Ferrucci, Luigi [2 ]
机构
[1] Univ Genoa, AOU IRCCS San Martino IST, Dept Internal Med, Genoa, Italy
[2] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA
[3] Vrije Univ Amsterdam, Med Ctr GGZ inGeest, Dept Psychiat, Amsterdam, Netherlands
[4] Vrije Univ Amsterdam, Med Ctr GGZ inGeest, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands
[5] AOU IRCCS San Martino IST, Dept Lab Med, Genoa, Italy
[6] Natl Inst Aging, Human Cardiovasc Studies Unit, Lab Cardiovasc Sci, NIH, Baltimore, MD USA
关键词
IGF-1; Vitamin D; Intima-media thickness; Aging; Atherosclerosis; Endothelial; 25-HYDROXYVITAMIN D CONCENTRATION; CARDIOVASCULAR RISK-FACTORS; FACTOR BINDING PROTEIN-3; HUMAN ENDOTHELIAL-CELLS; VASCULAR SMOOTH-MUSCLE; TUMOR-NECROSIS-FACTOR; APOE-DEFICIENT MICE; IGF-I; OXIDATIVE STRESS; PARATHYROID-HORMONE;
D O I
10.1016/j.atherosclerosis.2014.08.022
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (beta -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 (beta -0.214, p = 0.02) or 26 ng/mL (beta -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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:418 / 425
页数:8
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