title: Immunohistochemical profile of HIF-1α, VEGF-A, VEGFR2 and MMP9 proteins in tegumentary leishmaniasis.
abstract: BACKGROUND
  Leishmaniasis is one of the most important infectious diseases worldwide. Our study can provide more knowledge about angiogenic and hypoxic events in leishmaniasis. We attempted to verify whether the HIF-1 α protein expression may be associated to VEGF-A, VEGFR2 and MMP9 in leishmanial lesions.
  
  
  OBJECTIVE
  Besides understanding the pathway, we performed the correlation of VEGF-A, VEGFR2 and MMP9 proteins.
  
  
  METHODS
  In this study, we gathered 54 paraffin blocks taken from skin lesions in patients from northern Minas Gerais, Brazil, with confirmed diagnosis of tegumentary leishmaniasis. Immunohistochemistry was used to evaluate the expression of the proteins. The expression of HIF-1α was categorized into two groups according to the median: HIF-1 α lower and HIF-1 α higher.
  
  
  RESULTS
  We observed increase of VEGFR2 and MMP9 protein expressions in HIF-1 α higher group of epithelial cells. Spearman analyses in epithelial cells showed correlation between VEGF-A and MMP9, VEGFR2 and MMP9 protein expression.
  
  
  CONCLUSIONS
  HIF-1 α higher group showed increase of VEGFR2 and MMP9 proteins. In epithelial cells, VEGF-A was correlated to MMP9 protein. Furthermore, considering leukocyte cells, VEGFR2 was negatively correlated to MMP9 protein levels. This pathway possibly prepares the cells for a higher activity in a hypoxic or an angiogenic microenvironment. Other in vitro and in vivo studies may clarify the activation mechanism and the response from the proteins HIF-1 α, VEGFR2 and MMP-9 in tegumentary leishmaniasis.
authors.affiliation: Universidade Estadual de Montes Claros, MG, Brazil.
authors.forename: Carlos Alberto de Carvalho
authors.initials: CA
authors.lastname: Fraga
authors.forename: Marcos Vinicius Macedo de
authors.initials: MV
authors.lastname: Oliveira
authors.forename: Lucas Rodrigues
authors.initials: LR
authors.lastname: Alves
authors.forename: Agostinho Gonçalves
authors.initials: AG
authors.lastname: Viana
authors.forename: Adriana Alkmin de
authors.initials: AA
authors.lastname: Sousa
authors.forename: Sílvio Fernando Guimarães
authors.initials: SF
authors.lastname: Carvalho
authors.forename: Alfredo Maurício Batista
authors.initials: AM
authors.lastname: De Paula
authors.forename: Ana Cristina de Carvalho
authors.initials: AC
authors.lastname: Botelho
authors.forename: André Luiz Sena
authors.initials: AL
authors.lastname: Guimarães
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D016773:Leishmaniasis, Cutaneous / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D020780:Matrix Metalloproteinase 9