Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL
Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL
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DOI：
10.1152/ajpheart.2001.280.3.h1051
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发表时间：
2001-03-01
影响因子：
4.8
通讯作者：
Spaan, JAE
中科院分区：
文献类型：
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作者：
Constantinescu, AA;Vink, H;Spaan, JAE
与内皮细胞糖萼结合的蛋白聚糖和血浆蛋白对血管功能至关重要，但同时，它们通过减少流动血液可用的毛细血管体积来降低毛细管血细胞比容。因为氧化的低密度脂蛋白（oxLDL）降低了糖萼的有效厚度（Vink H，Constantinescu AA，and Spaan JAE.循环101：1500-1502，2000），我们设计了本研究以确定这是由糖萼成分的病理性降解引起的还是由流动血液的剪切力升高引起的糖萼变形增加引起的。用活体显微镜观察了24只仓鼠在全身给予正常低密度脂蛋白（n = 4）、中度氧化低密度脂蛋白（CuSO_4氧化6小时，n = 7）、重度氧化低密度脂蛋白（18小时氧化，n = 5）和中度氧化低密度脂蛋白加超氧化物歧化酶（SOD）和过氧化氢酶（n = 8）后右提睾肌的肌帽。中度oxLDL和重度oxLDL后，毛细管红细胞压积分别从0.16 +/- 0.03增加到0.37 +/- 0.05和从0.15 +/- 0.01增加到0.31 +/- 0.03。在解剖毛细血管直径没有变化的情况下，中度oxLDL和重度oxLDL后红细胞流量分别从8.7 +/- 1.9增加到13.8 +/- 3和从10.7 +/- 2.1增加到16.3 +/- 3.2个细胞/秒，证实了这些变化。红细胞速度，作为衡量的剪切力的glycocalyx，不受oxLDL，而组织预处理与SOD和过氧化氢酶完全废除oxLDL的影响glycocalyx厚度，毛细血管血细胞比容，和红细胞流量。我们得出结论，毛细血管红细胞压积升高oxLDL反映了氧自由基的内皮糖萼降解。
Proteoglycans and plasma proteins bound to the endothelial cell glycocalyx are essential for vascular function, but at the same time, they lower capillary tube hematocrit by reducing capillary volume available to flowing blood. Because oxidized low-density lipoproteins (oxLDL) reduce the effective thickness of the glycocalyx (Vink H, Constantinescu AA, and Spaan JAE. Circulation 101: 1500-1502, 2000), we designed the present study to determine whether this is caused by pathological degradation of glycocalyx constituents or increased glycocalyx deformation by elevated shear forces of flowing blood. Capillaries from the right cremaster muscle of 24 hamsters were examined by using intravital microscopy after systemic administration of normal LDL (n = 4), moderate oxLDL (6-h oxidation with CuSO4, n = 7), severe oxLDL (18-h oxidation, n = 5), and moderate oxLDL plus superoxide dismutase (SOD) and catalase (n = 8). Capillary tube hematocrit increased from 0.16 +/- 0.03 to 0.37 +/- 0.05 and from 0.15 +/- 0.01 to 0.31 +/- 0.03 after moderate oxLDL and severe oxLDL, respectively. These changes were paralleled by increases in red blood cell flux from 8.7 +/- 1.9 to 13.8 +/- 3 and from 10.7 +/- 2.1 to 16.3 +/- 3.2 cells/s after moderate oxLDL and severe oxLDL, respectively, in the absence of changes in anatomic capillary diameter. Red blood cell velocity, as a measure for the shear forces on the glycocalyx, was not affected by oxLDL, whereas tissue pretreatment with SOD and catalase completely abolished the effects of oxLDL on glycocalyx thickness, capillary hematocrit, and red blood cell flux. We conclude that elevation of capillary tube hematocrit by oxLDL reflects degradation of the endothelial glycocalyx by oxygen-derived free radicals.