Elevated Levels of Plasma Angiogenic Factors Are Associated with Human Lymphatic Filarial Infections

• Published in: The American journal of tropical medicine and hygiene Vol. 83; no. 4; pp. 884 - 890
• Main Authors: Bennuru, Sasisekhar, Maldarelli, Grace, Kumaraswami, V., Klion, Amy D., Nutman, Thomas B.
• Format: Journal Article
• Language: English
• Published: Deerfield, IL American Society of Tropical Medecine and Hygiene 01.10.2010; The American Society of Tropical Medicine and Hygiene
• Subjects: Adolescent; Adult; Aged; Angiogenic Proteins - blood; Angiogenic Proteins - metabolism; Angiopoietins - blood; Angiopoietins - metabolism; Animals; Biological and medical sciences; Diseases caused by nematodes; Doxycycline - therapeutic use; Elephantiasis, Filarial - blood; Elephantiasis, Filarial - drug therapy; Elephantiasis, Filarial - epidemiology; Elephantiasis, Filarial - parasitology; Fibroblast Growth Factor 2 - blood; Fibroblast Growth Factor 2 - metabolism; Filariases; Filaricides - therapeutic use; Helminthic diseases; Humans; India - epidemiology; Infectious diseases; Lymphatic filariases; Mali - epidemiology; Medical sciences; Middle Aged; Parasitic diseases; Vascular Endothelial Growth Factors - blood; Vascular Endothelial Growth Factors - metabolism; Wuchereria bancrofti; Young Adult; Mali; India; Infection; Human; Lymphatic system; Angiogenic factor; Lymph node; Nematode disease; Lymphatic; Tropical medicine; Parasitosis; Filariosis; Helminthiasis; Blood plasma
• ISSN: 0002-9637; 1476-1645; 1476-1645
• DOI: 10.4269/ajtmh.2010.10-0039

Lymphatic dilatation, dysfunction, and lymphangiogenesis are hallmarks of patent lymphatic filariasis, observed even in those with subclinical microfilaremia, through processes associated, in part, by vascular endothelial growth factors (VEGFs). A panel of pro-angiogenic factors was measured in the plasma of subjects from filaria-endemic regions using multiplexed immunological assays. Compared with endemic normal control subjects, those with both subclinical microfilaremia, and those with longstanding lymphedema had significantly elevated levels of VEGF-A, VEGF-C, VEGF-D, and angiopoeitins (Ang-1/Ang-2), with only levels of basic fibroblast growth factor (bFGF) and placental growth factor (PlGF) being elevated only if lymphedema was evident. Furthermore, levels of these factors 1-year post-treatment with doxycycline were similar to pretreatment levels suggesting a minimal role, if any, for Wolbachia . Our data support the concept that filarial infection per se is associated with elevated levels of most of the known pro-angiogenic factors, with only a few being associated with the serious pathologic consequences associated with Wuchereria bancrofti infection.