Department of Surgery, Center for Translational Injury Research, University of Texas Health Science Center, Houston, TX, USA.
Department of Biomedical Engineering, Wake Forest University, 575 N. Patterson Ave, Suite 120, Winston-Salem, NC, 27101, USA.
J Transl Med. 2015 Apr 12;13:117. doi: 10.1186/s12967-015-0481-5.
The endothelial glycocalyx layer (EGL) is a key regulator of vascular permeability, cell adhesion, and inflammation. The EGL is primarily composed of syndecan-1, hyaluronic acid (HA), heparan sulfate (HS) and chondroitin sulfate (CS). While many studies have observed increased shedding of syndecan-1 during hemorrhagic shock, little is known about the shedding of other EGL components, and their effects on altered permeability and coagulation. We characterized shedding of all four primary components of the EGL, as well as the plasma's effect on permeability and thrombin generation in a cohort of trauma patients.
Plasma samples were collected from 5 healthy consented volunteers and 22 severely injured trauma patients upon admission to the emergency department. ELISA assays were performed to quantify shed HA, HS, CS and syndecan-1 in plasma. A colloid osmometer and Electric Cell-substrate Impedance Sensing (ECIS) system were used to measure plasma colloid osmotic pressure (COP) and cell permeability, respectively. Thrombin generation was measured using a calibrated automated thrombogram (CAT). Initial vital signs, routine laboratory values, and injury severity scores (ISS) were recorded. Non-parametric statistical tests were used to compare differences between groups.
We observed increased shedding of all four proteins in trauma patient plasma compared to healthy controls: 31.7 vs. 21.2 U/L of CS, 175.8 vs. 121.9 ng/ml of HS, 946.7 vs. 618.6 ng/ml of HA and 245.8 vs. 31.6 ng/ml of syndecan-1 (all p<0.05). Patients with low plasma COP (≤16 mmHg) had significantly increased syndecan-1 and HA compared to those with normal COP, which corresponded to increased cell permeability via ECIS. CS and HS did not vary between COP groups. Lastly, patients with low COP displayed reduced peak thrombin generation of less than 250 nM on average (p<0.05).
Glycocalyx components were shed more in trauma patients compared to healthy controls in this cohort. However, only syndecan-1 and HA shedding were significantly higher in patients with reduced plasma COP. Thrombin generation was impaired in patients with low plasma COP. These data suggest that low plasma COP correlates well to glycocalyx degradation and thrombin loss following trauma, which consequently affect permeability and coagulation.
内皮糖萼层（EGL）是血管通透性、细胞黏附和炎症的关键调节因子。EGL 主要由 syndecan-1、透明质酸（HA）、肝素硫酸盐（HS）和软骨素硫酸盐（CS）组成。虽然许多研究观察到出血性休克期间 syndecan-1 的脱落增加，但对其他 EGL 成分的脱落及其对通透性和凝血改变的影响知之甚少。我们描述了 EGL 的所有四个主要成分的脱落，以及血浆对创伤患者群体通透性和凝血酶生成的影响。
从 5 名健康志愿者和 22 名严重创伤患者入院时收集血浆样本。使用 ELISA 测定法测定血浆中脱落的 HA、HS、CS 和 syndecan-1 的含量。使用胶体渗透压计和电动细胞-基质阻抗传感（ECIS）系统分别测量血浆胶体渗透压（COP）和细胞通透性。使用校准的自动血栓图（CAT）测量凝血酶生成。记录初始生命体征、常规实验室值和损伤严重程度评分（ISS）。使用非参数统计检验比较组间差异。
与健康对照组相比，我们观察到创伤患者血浆中所有四种蛋白的脱落增加：CS 为 31.7 vs. 21.2 U/L，HS 为 175.8 vs. 121.9 ng/ml，HA 为 946.7 vs. 618.6 ng/ml，syndecan-1 为 245.8 vs. 31.6 ng/ml（均<0.05）。COP（≤16mmHg）低的患者与 COP 正常的患者相比，syndecan-1 和 HA 显著增加，这与 ECIS 所示的细胞通透性增加相对应。CS 和 HS 在 COP 组之间没有差异。最后，COP 低的患者平均平均（p<0.05）的峰值凝血酶生成低于 250nM。
在该队列中，与健康对照组相比，创伤患者的糖萼成分脱落更多。然而，只有 COP 低的患者的 syndecan-1 和 HA 脱落明显更高。CO 低的患者凝血酶生成受损。这些数据表明，CO 低与创伤后糖萼降解和凝血酶丢失密切相关，从而影响通透性和凝血。
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