Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan.
Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan.
Diabetes Res Clin Pract. 2018 Feb;136:124-133. doi: 10.1016/j.diabres.2017.11.028. Epub 2017 Dec 14.
Renal dysfunction in addition to diabetes is a serious risk factor for cardiovascular events. We hypothesized that some of the changes in gene expression in blood cells cause renal dysfunction and macrovascular disease through impaired endothelial function. This study aimed to define which changes in gene expression in peripheral blood mononuclear cells (PBMCs) are related to renal function parameters and endothelial function of large arteries in patients with type 2 diabetes mellitus (T2DM).
We recruited 95 patients with T2DM. After matching for gender, age, BMI and HbA1c levels, the patient cohort included 42 with normoalbuminuria, 28 with microalbuminuria, and 25 with macroalbuminuria. All patients in the three groups were assessed for urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), flow-mediated dilatation (FMD), and mRNA expression in PBMCs.
The mRNA expression of platelet activating factor receptor (PAFR) differed most markedly between the three groups and was significantly higher in the macroalbuminuric group (p < 0.001 vs. normoalbuminuric group; p < 0.05 vs. microalbuminuric group). PAFR mRNA expression significantly correlated with log transformed ACR (ρ = 0.424, p < 0.001) but not eGFR. PAFR mRNA expression also had a significant negative correlation with FMD (ρ = -0.379, p < 0.001). Furthermore, the prevalence of macrovascular complications, particularly stroke, was significantly higher in patients with elevated PAFR mRNA expression in PBMCs.
PAFR overexpression in PBMCs may link diabetic nephropathy to macroangiopathy through impairment of endothelial function in patients with T2DM.
除糖尿病以外的肾功能障碍是心血管事件的严重危险因素。我们假设，血细胞中某些基因表达的改变通过损伤内皮功能导致肾功能障碍和大血管疾病。本研究旨在确定外周血单个核细胞（PBMC）中哪些基因表达的改变与 2 型糖尿病（T2DM）患者的肾功能参数和大动脉内皮功能相关。
我们招募了 95 例 T2DM 患者。在匹配性别、年龄、BMI 和 HbA1c 水平后，患者队列包括 42 例正常白蛋白尿、28 例微量白蛋白尿和 25 例大量白蛋白尿患者。所有三组患者均进行尿白蛋白/肌酐比值（ACR）、估算肾小球滤过率（eGFR）、血流介导的扩张（FMD）和 PBMC 中 mRNA 表达的评估。
三组之间血小板激活因子受体（PAFR）的 mRNA 表达差异最显著，且在大量白蛋白尿组中明显升高（p<0.001 与正常白蛋白尿组相比；p<0.05 与微量白蛋白尿组相比）。PAFR mRNA 表达与经对数转换的 ACR 显著相关（ρ=0.424，p<0.001），但与 eGFR 无关。PAFR mRNA 表达与 FMD 呈显著负相关（ρ=-0.379，p<0.001）。此外，在 PBMCs 中 PAFR mRNA 表达升高的患者中，大血管并发症（尤其是中风）的发生率明显更高。
在 T2DM 患者中，PBMCs 中 PAFR 过表达可能通过损伤内皮功能将糖尿病肾病与大血管疾病联系起来。
