title: Circulating Angiogenic Factors as Biomarkers of Disease Severity and Bacterial Burden in Pulmonary Tuberculosis.
abstract: BACKGROUND
  Angiogenesis and lymphangiogenesis are classical features of granuloma formation in pulmonary tuberculosis (PTB). In addition, the angiogenic factor--VEGF-A is a known biomarker for PTB.
  To examine the association of circulating angiogenic factors with PTB, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3in individuals with PTB, latent TB (LTB) or no TB infection (NTB).
  
  
  RESULTS
  Circulating levels of VEGF-A, VEGF-C andVEGF-R2 were significantly higher in PTB compared to LTB or NTB individuals. Moreover, the levels of VEGF-A, VEGF-C and VEGF-R2 were significantly higher in PTB with bilateral and/or cavitary disease. The levels of these factors also exhibited a significant positive relationship with bacterial burdens in PTB. ROC analysis revealed VEGF-A and VEGF-R2 as markers distinguishing PTB from LTB or NTB. Finally, the circulating levels of all the angiogenic factors examined were significantly reduced following successful chemotherapy.
  
  
  CONCLUSIONS
  Therefore, our data demonstrate that PTB is associated with elevated levels of circulating angiogenic factors, possibly reflecting vascular and endothelial dysfunction. In addition, some of these circulating angiogenic factors could prove useful as biomarkers to monitor disease severity, bacterial burden and therapeutic responses.
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Nathella Pavan
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Vaithilingam V
authors.initials: VV
authors.lastname: Banurekha
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Dina
authors.initials: D
authors.lastname: Nair
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000293:Adolescent; D000328:Adult; D042501:Angiogenic Proteins / Q000097:blood*; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D006801:Humans; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000302:isolation & purification; D009389:Neovascularization, Pathologic / Q000097:blood / Q000209:etiology; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D042582:Vascular Endothelial Growth Factor C / Q000097:blood; D042643:Vascular Endothelial Growth Factor D / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000097:blood; D055815:Young Adult
chemical_list: D042501:Angiogenic Proteins; D000995:Antitubercular Agents; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; C581309:FLT4 protein, human; C000588866:KDR protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3