Wang S Keisin, Green Linden A, Gutwein Ashley R, Kenyon Bianca, Motaganahalli Raghu L, Fajardo Andres, Gupta Alok K, Murphy Michael P
Department of Surgery, Division of Vascular Surgery, Indiana University School of Medicine, Indianapolis, USA.
Vascular. 2018 Dec;26(6):608-614. doi: 10.1177/1708538118777657. Epub 2018 Jun 5.
The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth.
Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4 cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4 cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments.
Peripheral blood was isolated from 266 patients without diabetes mellitus ( n=182), with diabetes mellitus not treated with metformin ( n=34), and with diabetes mellitus actively taking metformin ( n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4 fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1β, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-β. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics.
Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment.
在人群研究中反复观察到糖尿病对腹主动脉瘤形成和生长具有保护作用，但对此仍知之甚少。然而，最近的研究表明，二甲双胍作为一种主要的降糖药物，可能对腹主动脉瘤的形成和生长具有独立的保护作用。因此，我们描述了二甲双胍对腹主动脉瘤及高危患者炎症标志物的影响，炎症是腹主动脉瘤早期形成和生长的驱动因素。
采集先前诊断为腹主动脉瘤或因美国预防服务工作组推荐的腹主动脉瘤筛查前来就诊的患者的外周血。使用Ficoll密度离心法分离血浆和循环外周血单个核细胞。采用酶联免疫吸附测定法评估循环血浆中的炎症和调节细胞因子。使用流式细胞术分析进行CD4细胞表型分析，并表示为总CD4细胞的比例。为了确定针对自身抗原反应的循环抗体，针对抗V型胶原和弹性蛋白片段的抗体进行了改良的酶联免疫吸附测定。
2015年至2017年，从266例患者中分离出外周血，其中无糖尿病患者（n = 182）、未使用二甲双胍治疗的糖尿病患者（n = 34）以及正在积极服用二甲双胍的糖尿病患者（n = 50）。我们发现±二甲双胍的糖尿病患者中Tr1、Th17和Treg CD4亚群的表达没有差异。比较炎症细胞因子时，我们未检测到IL-1β、IL-6、IL-17、IL-23、IFN-γ和TNF-α的差异。相反，在调节细胞因子IL-4、IL-10、IL-13、TSG-6或TGF-β的表达方面未观察到差异。最后，在糖尿病患者中使用二甲双胍后，未检测到V型胶原和弹性蛋白片段抗原和/或抗体表达的差异。
对于有腹主动脉瘤风险或已诊断为腹主动脉瘤的糖尿病患者，二甲双胍似乎不会改变外周炎症环境。
