title: 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.
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy. Electronic address: pietroameri@unige.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ameri
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy; Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Canepa
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fabbi
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Leoncini
authors.affiliation: Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA; Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
authors.affiliation: Department of Laboratory Medicine, AOU-IRCCS San Martino-IST, Genova, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Mussap
authors.affiliation: Laboratory of Cardiovascular Sciences, Human Cardiovascular Studies Unit, National Institute on Aging, NIH, Baltimore, MD, USA.
authors.forename: Majd
authors.initials: M
authors.lastname: AlGhatrif
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy.
authors.forename: Manrico
authors.initials: M
authors.lastname: Balbi
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Viazzi
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Murialdo
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pontremoli
authors.affiliation: Department of Internal Medicine, AOU-IRCCS San Martino-IST, University of Genova, Genova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Brunelli
authors.affiliation: Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood; D000419:Albuminuria / Q000097:blood / Q000453:epidemiology; D000450:Aldosterone / Q000097:blood; D017209:Apoptosis; D015142:Baltimore / Q000453:epidemiology; D015992:Body Mass Index; D059168:Carotid Intima-Media Thickness; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005215:Fasting / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000453:epidemiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000494:pharmacology; D007558:Italy / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000502:physiology
chemical_list: D000450:Aldosterone; D006442:Glycated Hemoglobin; D007334:Insulin-Like Growth Factor I; D008055:Lipids; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D
keywords: Aging; Atherosclerosis; Endothelial; IGF-1; Intima-media thickness; Vitamin D