Department of Angiology, Systemic Hypertension, and Diabetology, Wroclaw Medical University, Wroclaw, Poland.
J Physiol Pharmacol. 2013 Aug;64(4):521-7.
The increased cardiovascular risk in type 2 diabetes mellitus (DM2) is the result of disorders of the immune system, including the enhanced reactivity of monocytes and impaired secretion of inflammatory cytokines. The aim of this study was to analyze the expression of calcium-sensing receptor (CaR) in peripheral blood monocytes of individuals with DM2 and peripheral artery disease (PAD). The study included 88 individuals, among them 37 patients with PAD (group A--atherosclerosis), 27 individuals with DM2 and PAD (group AD--atherosclerosis and diabetes mellitus), and 24 controls (group C--controls). The expression of CaR on isolated peripheral blood monocytes was analyzed at the level of surface protein (CaR(surf)) and mRNA (CaR(mRNA)). Concentrations of pro-inflammatory cytokines were determined by means of ELISA, while the severity of PAD was assessed with Doppler and impedance plethysmography. The expression of CaR(surf) was the highest in the controls (mean 41.27%) and did not differ significantly as compared to individuals from group AD (35.66%); however it was significantly higher than in group A (24.49%). The expression of CaR(surf) was related to the severity of PAD, fasting concentration of glucose, and the concentration of monocyte chemotactic protein (MCP-1). Additionally, significant differences were observed with regards to CaR(mRNA) expression; although, no significant relationships were documented between CaR(mRNA) and laboratory or clinical variables. Different ways of CaR(surf) and CaR(mRNA) expression regulation were associated with the concentration of osteopontin.
A nearly 1.5-fold higher expression of CaR(surf) on the peripheral blood monocytes of individuals with diabetes and PAD manifests during post-transcription stage and depends on fasting glucose concentration and MCP-1 concentration on one hand, and the severity of PAD on the other.
分析 2 型糖尿病(DM2)合并外周动脉疾病(PAD)患者外周血单核细胞中钙敏感受体(CaR)的表达。方法:本研究共纳入 88 例个体,其中 37 例合并 PAD(组 A-动脉粥样硬化),27 例合并 DM2 和 PAD(组 AD-动脉粥样硬化和糖尿病),24 例为对照组(组 C-对照组)。分析分离的外周血单核细胞表面蛋白(CaR(surf))和 mRNA(CaR(mRNA))水平的 CaR 表达。采用 ELISA 法测定促炎细胞因子浓度,多普勒和阻抗容积描记法评估 PAD 严重程度。结果:对照组 CaR(surf)表达最高(平均 41.27%),与 AD 组(35.66%)无显著差异,但明显高于 A 组(24.49%)。CaR(surf)表达与 PAD 严重程度、空腹血糖浓度和单核细胞趋化蛋白-1(MCP-1)浓度有关。此外,还观察到 CaR(mRNA)表达存在显著差异,但 CaR(mRNA)与实验室或临床变量之间无显著相关性。CaR(surf)和 CaR(mRNA)表达的不同调节方式与骨桥蛋白浓度有关。结论:DM2 合并 PAD 患者外周血单核细胞中 CaR(surf)的表达增加近 1.5 倍,发生在转录后阶段,一方面取决于空腹血糖浓度和 MCP-1 浓度,另一方面取决于 PAD 的严重程度。