Central Inter-Disciplinary Research Facility (CIDRF), School of Biological Science, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India.
Department of Information System and Analytics, National University of Singapore (NUS), Singapore, Republic of Singapore.
Transl Res. 2021 Jun;232:121-141. doi: 10.1016/j.trsl.2021.02.001. Epub 2021 Feb 7.
Plasma leakage is a hallmark process in dengue viral (DENV) infection that occurs due to the loss of vascular integrity in endothelial cells. Endoglin (ENG) and Syndecan-1 (SDC-1) are released by activated endothelial cells; however, the complete dynamics of its expression at the gene and protein levels during the course of DENV infection remains unknown. In the present study, we quantified the mRNA and soluble protein levels of ENG and SDC-1 in dengue cases during febrile, defervescence, and convalescence stages in Dengue without Warning Sign (DWOW-15), Dengue with Warning Sign (DWW-22), and Severe Dengue cases (SD-10) compared to nondengue Other Febrile Illness (OFI-10) and healthy control (HC-8). Respective protein and mRNA levels along with clinical characters were further analyzed for their efficacy in predicting disease outcomes using Support Vector Machine (SVM). We observed a steady and significant (P ≤ 0.01) increase in the levels of protein and mRNA of both the ENG and SDC-1 towards defervescence which is considered a critical phase in both severe and non-severe dengue cases. Importantly during the critical phase, the levels were significantly higher (P ≤ 0.001) in SD cases compared to DWW, DWOW, and OFI controls. However, at the time of admission (febrile), no such significant changes were observed within dengue, OFI, and healthy controls. SVM analysis revealed that the serum levels of ENG and SDC-1 along with other clinical symptoms could predict the disease severity with 100% accuracy. Based on the results we have proposed a mechanism on how ENG and SDC-1 could be involved in vascular dysfunction rather than just being a biomarker.
血浆渗漏是登革病毒（DENV）感染的一个标志过程，是由于内皮细胞血管完整性的丧失而发生的。内皮细胞激活时会释放内皮糖蛋白（ENG）和 syndecan-1（SDC-1）；然而，在 DENV 感染过程中，其基因和蛋白水平表达的完整动力学仍然未知。在本研究中，我们在 Dengue without Warning Sign（DWOW-15）、Dengue with Warning Sign（DWW-22）和重症登革热（SD-10）的发热、退热和恢复期阶段，定量检测了登革热病例中 ENG 和 SDC-1 的 mRNA 和可溶性蛋白水平，并与非登革热其他发热性疾病（OFI-10）和健康对照组（HC-8）进行了比较。进一步分析了相应的蛋白和 mRNA 水平以及临床特征，以使用支持向量机（SVM）预测疾病结局的疗效。我们观察到，在退热期，ENG 和 SDC-1 的蛋白和 mRNA 水平都呈稳定且显著（P ≤ 0.01）升高，这被认为是重症和非重症登革热病例的关键阶段。重要的是，在这个关键阶段，SD 病例的水平明显高于 DWW、DWOW 和 OFI 对照组（P ≤ 0.001）。然而，在登革热、OFI 和健康对照组中，在发热期（发热）并没有观察到这种显著变化。SVM 分析显示，ENG 和 SDC-1 的血清水平以及其他临床症状可以预测疾病的严重程度，准确率为 100%。根据结果，我们提出了一个关于 ENG 和 SDC-1 如何参与血管功能障碍的机制，而不仅仅是作为一个生物标志物。
