Inflammation determines the pro-adhesive properties of high extracellular d-glucose in human endothelial cells in vitro and rat microvessels in vivo.
Inflammation determines the pro-adhesive properties of high extracellular d-glucose in human endothelial cells in vitro and rat microvessels in vivo.
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DOI：
10.1371/journal.pone.0010091
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发表时间：
2010-04-08
期刊：
影响因子：
3.7
通讯作者：
Peiró C
中科院分区：
文献类型：
--
作者：
Azcutia V;Abu-Taha M;Romacho T;Vázquez-Bella M;Matesanz N;Luscinskas FW;Rodríguez-Mañas L;Sanz MJ;Sánchez-Ferrer CF;Peiró C
高血压被认为是发展糖尿病相关动脉粥样硬化的独立危险因素。目前，大多数治疗方法都是针对糖尿病患者的严格血糖控制，尽管这未能预防该疾病的大血管并发症。事实上，细胞外D-葡萄糖的升高是否能直接促进血管炎症，这有利于早期的动脉粥样硬化事件，这仍然是非常有争议的。在目前的工作中，增加细胞外D-葡萄糖从5.5到22 mmol/L既不足以诱导细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1）的表达，通过流式细胞术分析，也不足以促进白细胞粘附到人脐静脉内皮细胞（HUVEC）在体外，通过流动室测定。有趣的是，D-葡萄糖水平的升高增强了由促炎刺激（例如白细胞介素（IL）-1β（5 ng/mL））诱导的ICAM-1和VCAM-1表达以及白细胞粘附。在HUVEC中，高糖可增强IL-1β诱导的细胞外信号调节激酶1/2（ERK 1/2）和核转录因子-κB（NF-κB）的活化，但其本身无明显作用。ERK 1/2和NF-κB B对VCAM-1的表达是必需的，但对ICAM-1的表达不是必需的。在体内，白细胞运输进行了评价，在大鼠肠系膜微循环活体显微镜。与体外实验数据一致，急性腹腔注射D-葡萄糖可增加白细胞的滚动流量、粘附和迁移，但仅在IL-1β联合给药时才能增加。这些结果表明，细胞外D-葡萄糖水平的升高不足以促进血管炎症，并且它们突出了促炎环境在糖尿病中的关键作用，作为调节高血糖症的早期促动脉粥样硬化作用的关键因素。
Hyperglycemia is acknowledged as an independent risk factor for developing diabetes-associated atherosclerosis. At present, most therapeutic approaches are targeted at a tight glycemic control in diabetic patients, although this fails to prevent macrovascular complications of the disease. Indeed, it remains highly controversial whether or not the mere elevation of extracellular D-glucose can directly promote vascular inflammation, which favors early pro-atherosclerotic events. In the present work, increasing extracellular D-glucose from 5.5 to 22 mmol/L was neither sufficient to induce intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression, analyzed by flow cytometry, nor to promote leukocyte adhesion to human umbilical vein endothelial cells (HUVEC) in vitro, measured by flow chamber assays. Interestingly, the elevation of D-glucose levels potentiated ICAM-1 and VCAM-1 expression and leukocyte adhesion induced by a pro-inflammatory stimulus, such as interleukin (IL)-1β (5 ng/mL). In HUVEC, high D-glucose augmented the activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and nuclear transcription factor-κB (NF-κB) elicited by IL-1β, measured by Western blot and electromobility shift assay (EMSA), respectively, but had no effect by itself. Both ERK 1/2 and NF-κB were necessary for VCAM-1 expression, but not for ICAM-1 expression. In vivo, leukocyte trafficking was evaluated in the rat mesenteric microcirculation by intravital microscopy. In accordance with the in vitro data, the acute intraperitoneal injection of D-glucose increased leukocyte rolling flux, adhesion and migration, but only when IL-1β was co-administered. These results indicate that the elevation of extracellular D-glucose levels is not sufficient to promote vascular inflammation, and they highlight the pivotal role of a pro-inflammatory environment in diabetes, as a critical factor conditioning the early pro-atherosclerotic actions of hyperglycemia.
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影响因子：
158.5
作者：
Duckworth, William;Abraira, Carlos;Huang, Grant D.
通讯作者：
Huang, Grant D.
影响因子：
158.5
作者：
Holman, Rury R.;Paul, Sanjoy K.;Neil, H. Andrew W.
通讯作者：
Neil, H. Andrew W.
影响因子：
158.5
作者：
Gerstein, Hertzel C.;Miller, Michael E.;Friedewald, William T.
通讯作者：
Friedewald, William T.
影响因子：
7.7
作者：
Ceriello, A
通讯作者：
Ceriello, A
DOI：
10.1152/ajpendo.2000.279.4.e782
发表时间：
2000-10-01
影响因子：
5.1
作者：
Liu, WL;Schoenkerman, A;Lowe, WL
通讯作者：
Lowe, WL