Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study

Sophie Yacoub, Phung Khanh Lam, Trieu Trung Huynh, Hong Hanh Nguyen Ho, Hoai Tam Dong Thi, Nguyen Van Thu, Le Thi Lien, Quyen Nguyen Than Ha, Duyen Huynh Thi Le, Juthathip Mongkolspaya, Abigail Culshaw, Tsin Wen Yeo, Heiman Wertheim, Cameron Simmons, Gavin Screaton, Bridget Wills

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Abstract

Background Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however, the association of endothelial nitric oxide (NO) pathways with disease severity is unknown. 

Methods We performed a prospective observational study in 2 Vietnamese hospitals, assessing patients presenting early (<72 hours of fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability, was evaluated using peripheral artery tonometry (EndoPAT), and plasma levels of l-arginine, arginase-1, and asymmetric dimethylarginine were measured at serial time-points. The main outcome of interest was plasma leakage severity. 

Results Three hundred fourteen patients were enrolled; median age of the participants was 21(interquartile range, 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness. Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs 2.00; P <.001), over acute time-points, apparent already in the early febrile phase (1.29 vs 1.75; P =.012). RHI correlated negatively with arginase-1 and positively with l-arginine (P =.001). 

Conclusions Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininemia and high arginase-1 levels.

Original languageEnglish
Pages (from-to)1453-1461
Number of pages9
JournalClinical Infectious Diseases
Volume65
Issue number9
DOIs
Publication statusPublished - 1 Nov 2017
Externally publishedYes

Keywords

  • arginase
  • dengue
  • endothelial function
  • l -arginine
  • nitric oxide

Cite this

Yacoub, S., Lam, P. K., Huynh, T. T., Nguyen Ho, H. H., Dong Thi, H. T., Van Thu, N., Lien, L. T., Ha, Q. N. T., Le, D. H. T., Mongkolspaya, J., Culshaw, A., Yeo, T. W., Wertheim, H., Simmons, C., Screaton, G., & Wills, B. (2017). Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study. Clinical Infectious Diseases, 65(9), 1453-1461. https://doi.org/10.1093/cid/cix567