RESUMO
INTRODUCTION: Preeclampsia, a human pregnancy specific disorder is characterized by an anti-angiogenic state due to high levels of circulating soluble vascular endothelial growth factor 1 (sVEGFR1). However, the role of lymphangiogenesis in preeclampsia has not been investigated. Recently, impaired VEGF-C (factor that regulates lymphangiogenesis) signalling has been implicated in the pathogenesis of interstitial edema and salt-sensitive hypertension. OBJECTIVES: Therefore, we hypothesized that circulating VEGF-C and its circulating receptors (sVEGFR2 and sVEGFR3) may also be altered in preeclampsia and correlate with the severity of the phenotype. METHODS: We analyzed plasma levels of VEGF-C, sVEGFR1, sVEGFR2 and sVEGFR3 in women with gestational hypertension (GHTN, n=20), preeclampsia (PE, n=20) and normotensive pregnancies (NP, n=20) in the third trimester and values reported as mean±SD in pg/ml. RESULTS: As previously reported, sVEGFR1 levels were significantly higher in subjects with PE (19938 ± 12973) than in GHTN (7156±5432), p<0.01 or NP (7760±6018), p<0.01. VEGF-C levels were lower in subjects with GHTN (676±323) than in PE (1335±625), p<0.01, but not statistically different than in NP (971±556), p=0.11. There was a trend towards lower sVEGFR-2 in PE as compared to GHTN or NP. Interestingly sVEGFR-3 was significantly lower in PE (54,371±21,107) as compared to NP (83,709±24,983), p<0.01, but not different as compared to GHTN (54,642±26,947). The ratio of sVEGFR-2+sVEGFR-3/VEGF-C was dramatically lower during PE (57±38) as compared to GHTN (113±72), p<0.01 or NP (133±91), p<0.01. CONCLUSION: Preeclampsia is characterized by circulating pro-lymphangiogenic state as evidenced by decreased sVEGFR-3, slightly decreased VEGFR-2, increased VEGF-C and a dramatically lower ratio of sVEGFR2+sVEGFR3/VEGF-C. Our data suggests that the circulating pro-lymphoangiogenic state during preeclampsia may be a compensatory response to edema and hypertension. Additional studies are needed to evaluate the clinical relevance of the altered lymphangiogenic signalling pathway during preeclampsia.
