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.

Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury

“…6 Reduced expression of IGF-1 contributes to apoptosis of pulmonary fibroblasts 6 and endothelial cells. 48 Although we found that Cr supplementation increased the IGF-1 expression in bronchial epithelial cells and in pulmonary vascular cells, IGF-1 did not seen to play an important role in our I/R model. Furthermore, our results indicate that Cr may inhibit apoptosis of bronchial epithelial and endothelial cells, a phenomenon that involved in the formation of pulmonary edema.…”

Changes of serum 25(OH) D3 and IGF-1 levels in patients with thyroid nodules

“…Serum 25(OH)D3 may be partially protected by inhibition of inflammation (e.g., inhibition of abnormal angiogenesis and vascular endothelial dysfunction [22]). Besides, a previous study conducted in Italy revealed that circulation of IGF-1 is a major vascular protection factor at low circulation levels of vitamin D, and the mechanism is that IGF-1 strengthens the antioxidant and anti-apoptotic effects in endothelial cell culture [23]. Therefore, it can be concluded that the role of IGF-1 in disease is different.…”

IGF-1 and cardiovascular disease

“…Similarly, Kawachi et al [77] showed that IGF-1 levels were correlated with CC-IMT in non-obese individuals, and Splicke et al [78] showed a positive correlation between serum IGF-1/IGFBP-3 ratio and CC-IMT [77,78]. Ameri et al [79] found an interesting negative association of IGF-1 with CC-IMT only in patients in the lowest 25-hydroxyvitamin D quartile in the Baltimore Longitudinal Study of Aging (BLSA) and the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) study [79]. Abd El-Hafiz et al [80], in a comparative study of metabolically healthy obese individuals with healthy controls, also suggested that IGF-1 is protective against CC-IMT in the presence of low serum vitamin D [80].…”