Diab Vasc Dis Res. 2011 Jul;8(3):221-8. doi: 10.1177/1479164111415882. Epub 2011 Jul 11.
We investigated the associations of inflammatory blood cell activation with vascular parameters in patients with type 2 diabetes to elucidate the possible mechanisms of accelerated atherosclerosis observed in subjects with the Leucine 7 to Proline 7 polymorphism (Leu7Pro) in the neuropeptide Y (NPY).
Our study included 31 Caucasian patients with type 2 diabetes; 12 of them had the Leu7Pro7 (heterozygous), and 19 had the Leu7Leu7 (wild type) genotype. Vascular parameters were determined by ultrasound methods. Leukocyte analyses were performed from blood samples using flow cytometry. NPY concentrations were determined in plasma.
The amount of platelet-granulocyte complexes was positively correlated with NPY concentration (p=0.008) and carotid intima-media thickness (p=0.035) in the Leu7Pro7 group. Interferon gamma (IFN-γ) expression in monocytes correlated negatively with brachial artery flow-mediated dilatation also in the Leu7Pro7 group (p=0.037). The expression of tissue factor on monocytes correlated negatively with brachial artery diameter in the Leu7Pro7 patients as well (p=0.019).
The results indicate significant associations between inflammatory cell activation in blood and vascular atherosclerosis in genetically prone subjects, and provide possible mechanistic information about the role of NPY and the Leu7Pro polymorphism in the development of atherosclerosis.
本研究旨在探讨 2 型糖尿病患者炎症性血细胞激活与血管参数之间的相关性，以阐明在神经肽 Y（NPY）Leu7Pro 多态性（Leu7Pro）中存在脯氨酸 7 位亮氨酸（杂合子）的受试者中观察到的加速动脉粥样硬化的可能机制。
本研究纳入了 31 名高加索 2 型糖尿病患者；其中 12 名患者携带 Leu7Pro7（杂合子），19 名患者携带 Leu7Leu7（野生型）基因型。采用超声方法测定血管参数。采用流式细胞术从血液样本中进行白细胞分析。用放射免疫法测定血浆 NPY 浓度。
血小板-粒细胞复合物的数量与 Leu7Pro7 组中的 NPY 浓度（p=0.008）和颈动脉内膜中层厚度（p=0.035）呈正相关。单核细胞中干扰素γ（IFN-γ）的表达与 Leu7Pro7 组中的肱动脉血流介导的扩张也呈负相关（p=0.037）。单核细胞组织因子的表达与 Leu7Pro7 患者的肱动脉直径也呈负相关（p=0.019）。
这些结果表明，在遗传易感人群中，血液中炎症性细胞的激活与血管动脉粥样硬化之间存在显著相关性，并为 NPY 和 Leu7Pro 多态性在动脉粥样硬化发展中的作用提供了可能的机制信息。
