Elevated Levels of the Endothelial Molecules ICAM-1, VEGF-A, and VEGFR2 in Microscopic Asymptomatic Malaria

Abstract

Background In malaria, clinical disease has been associated with increased levels of endothelial activation due to the sequestration of infected erythrocytes. However, levels and impact of endothelial activation and pro-angiogenic molecules such as vascular endothelial growth factor (VEGF)-A and its receptor VEGFR2 in asymptomatic malaria have not been well characterized. Methods Blood samples were obtained from community children for malaria diagnosis using microscopy and PCR. A multiplex immunoassay was used to determine the levels of Intracellular adhesion molecule (ICAM)-1, VEGF-A, and VEGFR2 in the plasma of children with microscopic or submicroscopic asymptomatic parasitaemia and compared with levels in uninfected controls. Results Levels of ICAM-1, VEGF-A and VEGFR2 were significantly increased in children with microscopic asymptomatic parasitaemia compared with uninfected controls. Also, levels of VEGF-A were found to be inversely associated with age. Additionally, a receiver operating characteristic analysis revealed that plasma levels of ICAM-1 (AUC =0.72), showed a moderate potential in discriminating between children with microscopic malaria from uninfected controls when compared to VEGF-A (AUC =0.67) and VEGFR2 (AUC =0.69). Conclusion These data imply that endothelial activation and pro-angiogenic growth factors could be one of the early host responders during microscopic asymptomatic malaria, and may play a significant role in disease pathogenesis.

Intracellular adhesion molecule-1 and Vascular adhesion molecule-1 profile in uncomplicated malaria cases in Lagos, Nigeria

“…In this study, there was no association between parasite density and levels of ICAM-1 and VCAM-1. This is similar with the results of prior studies [15,16,19,20] which reported signi cant variances between uninfected controls and children with microscopic parasitaemia, but no signi cant correlation between parasite levels and these molecules.…”

“…In this study, the plasma concentrations of endothelial adhesion molecules; ICAM-1 and VCAM-1 were increased in cases with microscopic parasitaemia compared to uninfected controls. This nding aligns with previous studies [15,16,17], that reported an increase in ICAM-1 expression during malaria infections, and suggested its heightened binding with parasites displaying the appropriate Pf EMP-1 phenotype, indicating its potential signi cance in the development of cerebral malaria. It suggests that endothelial cells may react swiftly to the presence of the parasite in infected individuals, particularly when parasitaemia is visible by microscopy [15].…”

Evaluation of endothelial glycocalyx injury biomarkers in feline hemotropic mycoplasmosis

“…VEGF-A concentrations have been reported to be elevated in malaria and inflammatory diseases as a result of endothelial dysfunction 13 , 14 . In a recent study, there was no significant difference in VEGF-A concentrations between children with malaria and healthy ones 12 . Low concentrations have been associated with severe organ damage and mortality in sepsis, but it has not been a good indicator of prognosis 56 .…”

“…Endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) are heparanase activators responsible for the breakdown of heparan sulfate (HS), which constitutes 50% to 90% of the glycosaminoglycan (GAG) family expressed on the surface of endothelial cells 7 . On the other hand, vascular endothelial growth factor-A (VEGF-A) controls vascular permeability, proliferation, survival, and inflammation of endothelial cells 11 , 12 . Vascular endothelial growth factor-A concentrations have been shown to be elevated in inflammatory diseases that may be the result of endothelial dysfunction in human 13 , 14 .…”