Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Critical Care, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Crit Care. 2024 Apr 12;28(1):120. doi: 10.1186/s13054-024-04904-4.
Sepsis is associated with high morbidity and mortality, primarily due to systemic inflammation-induced tissue damage, resulting organ failure, and impaired recovery. Regulated extracellular matrix (ECM) turnover is crucial for maintaining tissue homeostasis in health and in response to disease-related changes in the tissue microenvironment. Conversely, uncontrolled turnover can contribute to tissue damage. Systemic Inflammation is implicated to play a role in the regulation of ECM turnover, but the relationship between the two is largely unclear.
We performed an exploratory study in 10 healthy male volunteers who were intravenously challenged with 2 ng/kg lipopolysaccharide (LPS, derived from Escherichia coli) to induce systemic inflammation. Plasma samples were collected before (T0) and after (T 1 h, 3 h, 6 h and 24 h) the LPS challenge. Furthermore, plasma was collected from 43 patients with septic shock on day 1 of ICU admission. Circulating neo-epitopes of extracellular matrix turnover, including ECM degradation neo-epitopes of collagen type I (C1M), type III (C3M), type IV (C4Ma3), and type VI (C6M), elastin (ELP-3) and fibrin (X-FIB), as well as the ECM synthesis neo-epitopes of collagen type III (PRO-C3), collagen type IV (PRO-C4) and collagen type VI (PRO-C6) were measured by ELISA. Patient outcome data were obtained from electronic patient records.
Twenty-four hours after LPS administration, all measured ECM turnover neo-epitopes, except ELP-3, were increased compared to baseline levels. In septic shock patients, concentrations of all measured ECM neo-epitopes were higher compared to healthy controls. In addition, concentrations of C6M, ELP-3 and X-FIB were higher in patients with septic shock who ultimately did not survive (N = 7) compared to those who recovered (N = 36).
ECM turnover is induced in a model of systemic inflammation in healthy volunteers and was observed in patients with septic shock. Understanding interactions between systemic inflammation and ECM turnover may provide further insight into mechanisms underlying acute and persistent organ failure in sepsis.
脓毒症与高发病率和死亡率相关，主要是由于全身炎症引起的组织损伤、导致器官衰竭和恢复受损。调节细胞外基质 (ECM) 的周转率对于维持健康组织的内稳态以及响应组织微环境中的疾病相关变化至关重要。相反，不受控制的周转率可能会导致组织损伤。全身性炎症被认为在 ECM 周转率的调节中发挥作用，但两者之间的关系在很大程度上尚不清楚。
我们在 10 名健康男性志愿者中进行了一项探索性研究，这些志愿者静脉内接受 2ng/kg 脂多糖 (LPS，源自大肠杆菌) 以诱导全身性炎症。在 LPS 挑战前 (T0) 和后 (T1 小时、3 小时、6 小时和 24 小时) 采集血浆样本。此外，还从入住 ICU 第 1 天的 43 名脓毒性休克患者中采集血浆。通过 ELISA 测量循环细胞外基质周转率的新表位，包括胶原 I 型 (C1M)、胶原 III 型 (C3M)、胶原 IV 型 (C4Ma3)、胶原 VI 型 (C6M)、弹性蛋白 (ELP-3) 和纤维蛋白 (X-FIB) 的 ECM 降解新表位，以及胶原 III 型 (PRO-C3)、胶原 IV 型 (PRO-C4) 和胶原 VI 型 (PRO-C6) 的 ECM 合成新表位。从电子病历中获取患者的预后数据。
在 LPS 给药后 24 小时，除 ELP-3 外，所有测量的 ECM 周转率新表位均高于基线水平。在脓毒性休克患者中，与健康对照组相比，所有测量的 ECM 新表位的浓度均较高。此外，最终未存活 (N=7) 的脓毒性休克患者的 C6M、ELP-3 和 X-FIB 浓度高于存活 (N=36) 的患者。
在健康志愿者的全身性炎症模型中诱导了 ECM 周转率，并且在脓毒性休克患者中观察到了 ECM 周转率。了解全身性炎症和 ECM 周转率之间的相互作用可能会进一步深入了解脓毒症中急性和持续性器官衰竭的机制。
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