title: Elevated levels of plasma angiogenic factors are associated with human lymphatic filarial infections.
abstract: 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 angiopoietins (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.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. bennurus@niaid.nih.gov
authors.forename: Sasisekhar
authors.initials: S
authors.lastname: Bennuru
authors.forename: Grace
authors.initials: G
authors.lastname: Maldarelli
authors.forename: V
authors.initials: V
authors.lastname: Kumaraswami
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000097:blood* / Q000378:metabolism; D042682:Angiopoietins / Q000097:blood / Q000378:metabolism; D000818:Animals; D004318:Doxycycline / Q000627:therapeutic use; D004605:Elephantiasis, Filarial / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000378:metabolism; D005369:Filaricides / Q000627:therapeutic use; D006801:Humans; D007194:India / Q000453:epidemiology; D008302:Mali / Q000453:epidemiology; D008875:Middle Aged; D042442:Vascular Endothelial Growth Factors / Q000097:blood / Q000378:metabolism; D014958:Wuchereria bancrofti; D055815:Young Adult
chemical_list: D042501:Angiogenic Proteins; D042682:Angiopoietins; D005369:Filaricides; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D004318:Doxycycline