Serum VEGF-D and VEGFR-3 are biomarkers in lymphangioleiomyomatosis for its diagnosis and impaired pulmonary function

Background: Lymphangioleiomyomatosis (LAM) is a disease characterized by proliferating LAM cells and LAM-associated lymphangiogenesis. Recently, it has been reported that the serum VEGF-D levels are increased in patients with LAM. Therefore, we hypothesized that VEGF-D and its receptor VEGFR-3 should be biomarkers for LAM. Objectives: To evaluate clinical significance of serum levels of VEGF-C, VEGF-D and VEGFR-3 in patients with LAM. Methods: We measured VEGF-C, VEGF-D and VEGFR-3 in serum of 7 patients with LAM, 4 patients with chronic obstructive pulmonary disease (COPD), and 6 normal subjects by enzyme-linked immunosorbent assays, and compared them with pulmonary function. Results: In patients with LAM, serum VEGF-D levels were significantly increased (2995.1±909.2 pg/ml) compared with patients with COPD and normal subjects (264.7±37.6 pg/ml, 444.9±153.7 pg/ml, respectively). Serum VEGFR-3 levels were also significantly increased in LAM (4511.3±746.7 pg/ml) compared with normal subjects (2633.8±304.1 pg/ml). In patients with LAM, serum VEGF-D levels were negatively correlated with FEV 1 /FVC (rs=-0.8630; p=0.0269) and%DLCO (rs=-0.9796; p=0.0035), and serum VEGFR-3 levels were negatively correlated with FEV 1 /FVC (rs=-0.8119; p=0.0498). Conclusion: These results indicate that, in LAM, serum VEGF-D and VEGFR-3 are candidate for biomarkers for the diagnosis and impaired pulmonary function.