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Increased shedding of PECAM-1 associated with elevated serum MMP-14 levels as new blood indicators of dengue disease manifestation - 16/10/24

Doi : 10.1016/j.idnow.2024.104964 
Vignesh Mariappan a , Lokesh Shanmugam b , Siva Ranganathan Green c , Joshy M Easow d , Srinivasa Rao Mutheneni e , Anitha Thirugnanasambandhar Sivasubramanian f , Agieshkumar Balakrishna Pillai a,
a Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607 402, India 
b ICMR-National Institute of Epidemiology (ICMR-NIE), Ayapakkam, Chennai 600 070, India 
c Department of General Medicine, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607 402, India 
d Department of Microbiology, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607 402, India 
e Division of Applied Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, Telangana 500 007, India 
f Department of Biochemistry and Molecular Biology, School of Life Science, Pondicherry University, Puducherry 605 014, India 

Corresponding author.

Highlights

The role of PECAM-1 in regulation of vascular integrity during viral diseases is poorly studied.
Increased shedding of PECAM-1 coupled with enhanced expression of MMP-14 was associated with plasma leakage during critical phase of dengue.
Elevated MMP-14 could be involved in proteolytic cleavage of membrane-bound PECAM-1 into the circulation.
Serum levels of sPECAM-1 & MMP-14 could serve as biomarkers for the early prognosis of dengue disease outcomes.
This is the first report to study the complete dynamics of PECAM-1 & MMP-14 during the three phases of dengue infection.

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Abstract

Objectives

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.

Patients and methods

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.

Results

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.

Conclusion

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.

Le texte complet de cet article est disponible en PDF.

Keywords : Dengue, Plasma Leakage, Thrombocytopenia, PECAM-1, Matrix Metalloproteinases


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Vol 54 - N° 7

Article 104964- octobre 2024 Retour au numéro
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