Opposed circulating plasma levels of endothelin-1 and C-type natriuretic peptide in children with Plasmodium falciparum malaria

Abstract

Background: Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria (SM), are not yet fully understood. Both endothelin-1 (ET-1) and C-type natriuretic peptide (CNP) are produced by vascular endothelium and act locally as paracrine regulators of vascular tone, ET-1 being a potent vasoconstrictor and CNP having strong vasorelaxant properties.

Methods: Plasma levels of ET-1 and N-terminal fragments of CNP (NT-proCNP) were studied on admission and after 24 hours of treatment, using enzyme-linked-immunosorbent-assay (ELISA) technique, in Gabonese children with severe falciparum malaria (SM, n = 50), with uncomplicated malaria (UM, n = 39) and healthy controls (HC, n = 25).

Results: Compared to HC, malaria patients had significantly higher plasma levels of ET-1 and significantly lower levels of NT-proCNP (p < 0.001 and p < 0.024 respectively). Plasma levels of NT-proCNP were additionally decreased in SM patients compared to HC (p = 0.034), whereas UM was not significantly different to HC. In the SM group we found a trend towards lower ET-1 levels compared to UM (p = 0.085).

Conclusion: In the present study, an imbalance between the vasoconstricitve and vasorelaxant endothelium-derived substances ET-1 and CNP in the plasma of children with falciparum malaria is demonstrated, presumably in favor of vasoconstrictive and pro-inflammatory effects. These results may indicate involvement of ET-1 and CNP in malaria pathogenesis. Furthermore, results of lower ET-1 and CNP levels in SM may reflect endothelial cell damage.

Figure 1

Endothelin-1 plasma levels. Circulating plasma levels of endothelin-1 (ET-1) in children with severe malaria (SM, square dots), uncomplicated malaria (UM, triangle dots) on admission to hospital and after 24 hours of treatment and healthy controls (HC, round dots), determined using ELISA-technique. Scatter plots, lines indicate Median values. Analyses by ANOVA, p-values were Bonferroni corrected for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001

Figure 2

NT-proCNP plasma levels. Circulating plasma levels NT-pro C-type natriuretic peptide (CNP) in children with severe malaria (SM, square dots), uncomplicated malaria (UM, triangle dots) on admission to hospital and after 24 hours of treatment and healthy controls (HC, round dots), determined using ELISA-technique. Scatter plots, lines indicate Median values. Analyses by ANOVA, p-values were Bonferroni corrected for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001