Evidence of Vascular Damage in Dengue Disease: Demonstration of High Levels of Soluble Cell Adhesion Molecules and Circulating Endothelial Cells

Abstract

Clinical evidence suggests that vascular damage plays a key role in the pathophysiology of dengue hemorrhagic fever (DHF). In this study, the authors tested this hypothesis by examining the levels of soluble intercellular adhesion molecule and vascular cell adhesion molecule (sICAM-1 and sVCAM-1), and the presence of circulating endothelial cells (CECs), as evidence of vascular damage, in peripheral blood from DHF patients (n=13). A significant increase in plasma levels of sICAM-1 (n=12) and sVCAM-1 (n=13) was detected by enzyme-linked immunosorbent assay (ELISA) in DHF patients, compared with healthy individuals. Increased numbers of CECs, as detected by the expression of endothelial cell markers (ICAM-1, platelet cell adhesion molecule [PCAM]-1, and CD36) with flow cytometry, were observed in DHF patients (n=4), compared to healthy subjects. The high levels of sICAM-1 and sVCAM-1, together with the presence of CECs in DHF patients, provide further evidence of endothelium damage and activation in DHF patients.

Markers of dengue severity: a systematic review of cytokines and chemokines

“…One promising example is TNFa, which was reported to induce endothelial cell apoptosis and was also noted in this review as an elevated cytokine in DHF. Other potential circulating markers of dengue severity, such as proteases (Koraka et al, 2010;St John et al, 2013;van de Weg et al, 2014), soluble adhesion molecules (Cardier et al, 2006) or metabolites (Cui et al, 2013(Cui et al, , 2016, may show potential as alternative soluble prognostic markers of SD, but face similar challenges in the extensive demands of large study cohorts. Capturing soluble factors that correlate and potentially foretell pathognomonic symptoms may not only increase the specificity and sensitivity of prognosing SD, but also avoid the non-specific 'cytokine storms' observed in other acute infectious diseases, such as influenza and malaria (Clark, 2007).…”

Dengue Virus Infection of Mast Cells Triggers Endothelial Cell Activation

“…Dengue virus infection promotes upregulation of membrane-associated and soluble adhesion molecules which are indicative of endothelial cell activation (1,36). These parameters correlate with disease severity (9,21,25,34,43).…”

“…Dengue virus infection promotes upregulation of membrane-associated and soluble adhesion molecules which are indicative of endothelial cell activation (1, 36). These parameters correlate with disease severity (9,21,25,34,43).Mast cells are connective tissue-associated leukocytes located at areas of external interface, such as the skin and mucous membranes. They are in close proximity to blood vessels, with functional roles in a variety of inflammatory conditions (i.e., asthma and allergy) and innate protection against pathogens.…”

“…A number of additional factors have been suggested to dysregulate endothelium in dengue disease. Vascular endothelial growth factor (VEGF) has been suggested to play a role in promoting vascular permeability in severe dengue disease (9,46). CXCL8 production by dengue virus-infected HMEC-1 cells contributes to virus-induced effects on cytoskeleton and tight junctions, influencing transendothelial permeability (45).…”

Effect of dengue virus infection on the permeability of vero cells line

“…It was revealed that 91% of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) patients have spontaneous bleeding manifestation and 79% of them have pleura effusion. Cardier et al [4] reported the presence of circulating endothelial cells in the peripheral blood as the evidence of vascular damage in DHF patients. An autopsy study of 63 years old male patient died due to DHF revealed tissue damaged, caused by intense haemorrhage, interstitial edema and inflammation.…”