Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
Atherosclerosis. 2014 Jan;232(1):25-30. doi: 10.1016/j.atherosclerosis.2013.10.024. Epub 2013 Oct 31.
Whether IGF-1 has a protective or a detrimental role in vascular homeostasis remains unsettled. There is evidence that the C/T polymorphism rs35767 near the promoter region of the IGF1 gene located in chromosome 12 is associated with plasma IGF-1 levels. We investigated the effects of this polymorphism on circulating IGF-1 levels, carotid intima media thickness (cIMT) and endothelial-dependent vasodilation.
Two samples of adult nondiabetic Whites were studied. Sample 1 comprised 1124 individuals in whom cIMT was measured by ultrasonography. Sample 2 included 162 drug-naïve hypertensive individuals in whom endothelium-dependent and endothelium-independent vasodilation were assessed by intra-arterial infusion of acetylcholine (ACh), and sodium nitroprusside (SNP), respectively. IGF-1 was determined by chemiluminescent immunoassay. rs35767 polymorphism was screened using a TaqMan allelic discrimination assay.
In sample 1, IGF-1 levels were higher in subjects carrying the T allele compared with CC carriers (178 ± 78 vs. 166 ± 60 ng/mL, respectively; P = 0.007 adjusted for age, gender, and BMI). cIMT was lower in subjects carrying the T allele compared with CC carriers (0.71 ± 0.20 vs. 0.76 ± 0.22 mm, respectively; P < 0.0001 adjusted for age, gender, and BMI). In sample 2, maximally ACh-stimulated forearm blood flow was higher in subjects carrying the T allele compared with CC carriers (343 ± 191 vs. 281 ± 125%, respectively; P = 0.02 adjusted for age, gender, and BMI).
Subjects carrying the T allele exhibited significantly higher levels of circulating IGF-1, lower values of cIMT, and higher endothelium-dependent vasodilatation compared with CC carriers. These findings support the idea that IGF-1 plays a role in the pathogenesis of atherosclerosis.
关于 IGF-1 在血管稳态中是发挥保护作用还是有害作用，目前仍未有定论。有证据表明，位于 12 号染色体上 IGF1 基因启动子区域附近的 C/T 多态性 rs35767 与血浆 IGF-1 水平有关。我们研究了这种多态性对循环 IGF-1 水平、颈动脉内膜中层厚度（cIMT）和内皮依赖性血管舒张的影响。
我们研究了两个非糖尿病白人成年人样本。样本 1 包括 1124 名通过超声测量 cIMT 的个体。样本 2 包括 162 名未经药物治疗的高血压个体，通过动脉内输注乙酰胆碱（ACh）和硝普钠（SNP）分别评估内皮依赖性和内皮非依赖性血管舒张。通过化学发光免疫测定法测定 IGF-1。使用 TaqMan 等位基因鉴别检测法筛选 rs35767 多态性。
在样本 1 中，与 CC 携带者相比，携带 T 等位基因的个体 IGF-1 水平更高（分别为 178±78 与 166±60 ng/mL；P=0.007，调整年龄、性别和 BMI）。与 CC 携带者相比，携带 T 等位基因的个体 cIMT 更低（分别为 0.71±0.20 与 0.76±0.22 mm；P＜0.0001，调整年龄、性别和 BMI）。在样本 2 中，与 CC 携带者相比，携带 T 等位基因的个体在 ACh 刺激下的前臂血流最大增加率更高（分别为 343±191 与 281±125%；P=0.02，调整年龄、性别和 BMI）。
与 CC 携带者相比，携带 T 等位基因的个体循环 IGF-1 水平显著升高，cIMT 值更低，内皮依赖性血管舒张功能更高。这些发现支持 IGF-1 在动脉粥样硬化发病机制中发挥作用的观点。
