Mariappan Vignesh, Shanmugam Lokesh, Ranganathan Green Siva, Easow Joshy M, Mutheneni Srinivasa Rao, Thirugnanasambandhar Sivasubramanian Anitha, Balakrishna Pillai Agieshkumar
Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607 402, India.
ICMR-National Institute of Epidemiology (ICMR-NIE), Ayapakkam, Chennai 600 070, India.
Infect Dis Now. 2024 Oct;54(7):104964. doi: 10.1016/j.idnow.2024.104964. Epub 2024 Aug 22.
Host factors that regulate plasma leakage during severe dengue (SD) are under investigation. While PECAM-1 and MMP-14 have been reported to regulate vascular integrity, their role in dengue pathogenesis remains unexplored. This study aims to assess the association of soluble PECAM-1 and MMP-14 with dengue severity symptoms.
Serum levels of PECAM-1 and MMP-14 were evaluated in dengue (N-25) comprising 10 severe dengue (SD) and 15 non-severe dengue, 10 other febrile illnesses along with healthy controls (N-10) using ELISA. Protein levels were assessed using in vitro models.
From febrile to critical phase, a significant increase in PECAM-1 (P≤0.01) & MMP-14 (P≤0.001) levels were observed in SD cases compared to non-severe or other controls. Serum levels of PECAM-1 and MMP 14 were found to be positively (P≤0.001) associated. Soluble PECAM-1 levels of severe defervescence showed a positive correlation (P≤0.001) with plasma leakage and an inverse relationship (P≤0.001) with platelet count. In vitro analysis revealed elevated expression of study proteins in endothelial cells activated with severe serum samples. To the best of our knowledge, this is the first report to explore PECAM-1 or MMP-14 dynamics and their association with dengue severity.
Higher shedding of sPECAM-1 accompanied with increased levels of MMP-14 is strongly associated with severe dengue. However, the exact role of serum PECAM-1 in disease prognosis requires further studies.
正在研究严重登革热（SD）期间调节血浆渗漏的宿主因素。虽然据报道PECAM-1和MMP-14可调节血管完整性，但其在登革热发病机制中的作用仍未得到探索。本研究旨在评估可溶性PECAM-1和MMP-14与登革热严重症状的关联。
采用酶联免疫吸附测定法（ELISA）评估了25例登革热患者（其中10例为严重登革热、15例为非严重登革热）、10例其他发热性疾病患者以及10例健康对照者血清中PECAM-1和MMP-14的水平。使用体外模型评估蛋白质水平。
从发热期到危重症期，与非严重登革热患者或其他对照相比，严重登革热患者的PECAM-1（P≤0.01）和MMP-14（P≤0.001）水平显著升高。发现PECAM-1和MMP 14的血清水平呈正相关（P≤0.001）。严重退热期的可溶性PECAM-1水平与血浆渗漏呈正相关（P≤0.001），与血小板计数呈负相关（P≤0.001）。体外分析显示，用严重血清样本激活的内皮细胞中研究蛋白的表达升高。据我们所知，这是第一份探索PECAM-1或MMP-14动态变化及其与登革热严重程度关联的报告。
sPECAM-1的较高脱落伴随着MMP-14水平的升高与严重登革热密切相关。然而，血清PECAM-1在疾病预后中的确切作用需要进一步研究。
