Laboratory for Atherosclerosis and Metabolic Research, Department of Medical Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA.
Cardiovasc Res. 2009 Dec 1;84(3):479-84. doi: 10.1093/cvr/cvp249. Epub 2009 Jul 20.
Inflammation is pivotal in atherosclerosis and a key early step is endothelial dysfunction. C-reactive protein, the prototypic marker of inflammation, and cardiovascular risk marker have been shown to promote atherogenesis. Increased levels of C-reactive protein are associated with endothelial dysfunction. The glycocalyx decorates the luminal surface and affords critical protection of the endothelium. Thus, the aim of the study was to examine the effect of C-reactive protein on the endothelial glycocalyx.
Human aortic endothelial cells (HAECs) were incubated with C-reactive protein at different concentrations (0, 12.5, 25, and 50 microg/mL) with boiled C-reactive protein as a control. For in vivo experiments, human C-reactive protein was injected into rats and human serum albumin was used as a control. Endothelial glycocalyx thickness was examined by transmission electron microscopy. Hyaluronan (HA) was examined in the supernatant of HAECs and in plasma and surface expression of heparan sulfate (HS) was quantified. C-reactive protein dose-dependently increased HA release in vitro and in vivo (P < 0.01). Also, glycocalyx thickness was significantly decreased (P < 0.05). Western blotting for HS showed significant reduction in expression of HS, one of the main glycosaminoglycans in the glycocalyx, with C-reactive protein treatment. There was a significant positive correlation between HA release and monocyte-endothelial cell adhesion, plasminogen activator inhibitor-1, and intercellular adhesion molecule-1 release and a negative correlation with endothelial nitric oxide synthase activity.
Collectively, these data suggest that C-reactive protein impairs glycocalyx function, resulting in endothelial dysfunction.
炎症在动脉粥样硬化中起着关键作用，而内皮功能障碍是其早期的关键步骤。C 反应蛋白作为炎症的典型标志物和心血管风险标志物，已被证明可促进动脉粥样硬化的形成。C 反应蛋白水平升高与内皮功能障碍有关。糖萼覆盖在管腔表面，为内皮提供关键的保护。因此，本研究旨在探讨 C 反应蛋白对内皮糖萼的影响。
将人主动脉内皮细胞（HAEC）分别用不同浓度（0、12.5、25 和 50μg/ml）的 C 反应蛋白孵育，以煮沸的 C 反应蛋白作为对照。在体内实验中，将人 C 反应蛋白注入大鼠体内，用人血清白蛋白作为对照。通过透射电子显微镜观察内皮糖萼的厚度。通过 HAEC 上清液和血浆检测透明质酸（HA），并定量检测表面硫酸乙酰肝素（HS）的表达。C 反应蛋白呈剂量依赖性地增加体外和体内的 HA 释放（P < 0.01）。同时，糖萼厚度明显降低（P < 0.05）。HS 的 Western blot 显示，C 反应蛋白处理后，HS 的表达明显减少，HS 是糖萼中主要的糖胺聚糖之一。HA 释放与单核细胞-内皮细胞黏附、纤溶酶原激活物抑制剂-1 和细胞间黏附分子-1 释放呈显著正相关，与内皮型一氧化氮合酶活性呈显著负相关。
综上所述，这些数据表明 C 反应蛋白损害了糖萼的功能，导致内皮功能障碍。
