Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo
Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo
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DOI：
10.2337/diabetes.55.02.06.db05-1103
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发表时间：
2006-02-01
期刊：
影响因子：
7.7
通讯作者：
Stroes, ESG
中科院分区：
文献类型：
--
作者：
Nieuwdorp, M;van Haeften, TW;Stroes, ESG
高血压与动脉粥样硬化血栓形成刺激的易感性增加有关。糖萼是一层覆盖在内皮上的蛋白多糖，参与了血管壁的保护能力。因此，我们评估高血糖是否影响糖萼，从而增加血管的脆弱性。通过比较10名健康男性受试者中糖萼渗透性示踪剂（右旋糖酐40）与糖萼非渗透性示踪剂（标记红细胞）的分布体积来估计全身糖萼体积。在五种情况下以随机顺序进行测量：两次对照测量、在有或没有N-乙酰半胱氨酸（NAC）输注的正常胰岛素高血糖期间进行两次测量，以及在甘露醇输注期间进行一次测量。糖萼测量结果具有重现性（1.7 +/- 0.2 vs. 1.7 +/- 0.3 l）。高血压使糖萼体积减少（至0.8 +/- 0.2 l; P < 0.05），NAC能够防止减少（1.4 +/- 0.2 l）。甘露醇输注对糖萼体积（1.6 +/- 0.1 l）无影响。高血压导致内皮功能障碍，血浆透明质酸水平升高（从70 +/- 6到112 +/- 16 ng/ml; P < 0.05）和凝血激活（凝血酶原活化片段1 + 2：从0.4 +/- 0.1到1.1 +/- 0.2 nmol/l; D-二聚体：从0.27 +/- 0.1到0.55 +/- 0.2 g/l; P < 0.05）。综上所述，这些数据表明，在高血糖期间，糖萼扰动在介导血管功能障碍中的潜在作用。
Hyperglycemia is associated with increased susceptibility to atherothrombotic stimuli. The glycocalyx, a layer of proteoglycans covering the endothelium, is involved in the protective capacity of the vessel wall. We therefore evaluated whether hyperglycemia affects the glycocalyx, thereby increasing vascular vulnerability. The systemic glycocalyx volume was estimated by comparing the distribution volume of a glycocalyx permeable tracer (dextran 40) with that of a glycocalyx impermeable tracer (labeled erythrocytes) in 10 healthy male subjects. Measurements were performed in random order on five occasions: two control measurements, two measurements during normoinsulinemic hyperglycemia with or without N-acetylcysteine (NAC) infusion, and one during mannitol infusion. Glycocalyx measurements were reproducible (1.7 +/- 0.2 vs. 1.7 +/- 0.3 l). Hyperglycemia reduced glycocalyx volume (to 0.8 +/- 0.2 l; P < 0.05), and NAC was able to prevent the reduction (1.4 +/- 0.2 l). Mannitol infusion had no effect on glycocalyx volume (1.6 +/- 0.1 l). Hyperglycemia resulted in endothelial dysfunction, increased plasma hyaluronan levels (from 70 +/- 6 to 112 +/- 16 ng/ml; P < 0.05) and coagulation activation (prothrombin activation fragment 1 + 2: from 0.4 +/- 0.1 to 1.1 +/- 0.2 nmol/l; D-dimer: from 0.27 +/- 0.1 to 0.55 +/- 0.2 g/l; P < 0.05). Taken together, these data indicate a potential role for glycocalyx perturbation in mediating vascular dysfunction during hyperglycemia.