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Concentration of Serum Vascular Endothelial Growth Factor (VEGF-D) and Its Correlation with Functional and Clinical Parameters in Patients with Lymphangioleiomyomatosis from a Brazilian Reference Center

  • Alexandre Franco Amaral
  • Martina Rodrigues de Oliveira
  • Olívia Meira Dias
  • Fábio Eiji Arimura
  • Carolina Salim Gonçalves Freitas
  • Milena Marques Pagliarelli Acencio
  • Vanessa Adélia de Alvarenga
  • Ronaldo Adib Kairalla
  • Carlos Roberto Ribeiro Carvalho
  • Bruno Guedes BaldiEmail author
  • Tuberous Sclerosis, Lymphangioleiomyomatosis and Angiomyolipoma Study Group, Universidade de Sao Paulo, Brazil



Serum vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that is considered a valuable tool in the diagnosis of lymphangioleiomyomatosis (LAM). Previous studies have reported a wide variability in VEGF-D serum levels in LAM patients and it seems to be associated with pulmonary impairment and lymphatic involvement.


We conducted a cross-sectional study from 2009 to 2017 that evaluated VEGF-D serum levels in a cohort of LAM patients who were never treated with mTOR inhibitors and compared them to healthy age-matched volunteers. Clinical and functional parameters were assessed and correlated with their respective serum VEGF-D levels.


One hundred and four patients were included in the analysis. Serum VEGF-D levels were higher in LAM patients compared to healthy controls: 796 (404–1588) versus 162 (117–232) pg/mL, respectively (p < 0.001). Patients with tuberous sclerosis complex–LAM, TSC–LAM (20%), had higher levels of VEGF-D when compared to patients with sporadic LAM (80%) [1005 (641–2732) vs. 772 (370–1383), p = 0.05]. Serum VEGF-D levels were weakly correlated with DLCO (r = − 0.26, p = 0.001) and lymphatic involvement was more frequent in those with serum VEGF-D levels equal or above 800 pg/mL (35% vs. 13%, p = 0.02).


In LAM, serum VEGF-D is weakly associated with lung function impairment and strongly associated with lymphatic involvement. VEGF-D is validated for use in Brazilian patients with LAM whose characteristics must be accounted for when evaluating their serum VEGF-D levels.


Interstitial lung disease Lymphangioleiomyomatosis Pulmonary function tests Vascular endothelial growth factor 



Other members of the Tuberous Sclerosis, Lymphangioleiomyomatosis and Angiomyolipoma Study Group include the following: Bruno Eduardo Pedroso Balbo, Elieser Hitoshi Watanabe, Luciana Paula Samorano, Luiz Fernando Onuchic, Maria Cecília da Matta Rivitti-Machado, Maria Luiza Giraldes de Manreza, Maurício Dener Cordeiro, Patrícia Takahashi, and Zilda Najjar Prado de Oliveira.


Financial support for this study was provided by Novartis Biociências S.A. Novartis had no participation whatsoever in the design, management, and analysis of data or in the decision to publish this study.

Compliance with Ethical Standards

Conflict of interest

The authors received no refunds or financial benefits and have no conflicts of interest to declare.

Supplementary material

408_2018_191_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Alexandre Franco Amaral
    • 1
  • Martina Rodrigues de Oliveira
    • 1
  • Olívia Meira Dias
    • 1
  • Fábio Eiji Arimura
    • 1
  • Carolina Salim Gonçalves Freitas
    • 1
  • Milena Marques Pagliarelli Acencio
    • 1
  • Vanessa Adélia de Alvarenga
    • 1
  • Ronaldo Adib Kairalla
    • 1
  • Carlos Roberto Ribeiro Carvalho
    • 1
  • Bruno Guedes Baldi
    • 1
    Email author return OK on get
  • Tuberous Sclerosis, Lymphangioleiomyomatosis and Angiomyolipoma Study Group, Universidade de Sao Paulo, Brazil
  1. 1.Divisao de Pneumologia, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de MedicinaUniversidade de Sao PauloSão PauloBrazil

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