Circulating Lymphangiogenic Factors in Preeclampsia

Abstract

Background 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 (sVEGFR-1). 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. Therefore, we hypothesized that circulating VEGF-C and its circulating receptors (sVEGFR-2 and sVEGFR-3) may also be altered in preeclampsia and correlate with the severity of the phenotype. Methods We analyzed plasma levels of VEGF-C, sVEGFR-1, sVEGFR-2 and sVEGFR-3 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, sVEGFR-1 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 (54371 ± 21107) as compared to NP (83709 ± 24983), p<0.01, but not different as compared to GHTN (54642 ± 26947). 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 sVEGFR-2, increased VEGF-C and a dramatically lower ratio of sVEGFR-2+sVEGFR-3/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.

The defect of both angiogenesis and lymphangiogenesis is involved in preeclampsia

“…A study found that PE is characterized by decreased soluble VEGFR3, slightly decreased soluble VEGFR2, and increased VEGFC in the plasma; the level of soluble VEGFR-3 in PE plasma is consistent with the expression of VEGFR3 in the decidua in the present study [40]. However, these works concluded that decreased soluble VEGFR3 (sVEGFR3), slightly decreased sVEGFR2, increased VEGF-C, and dramatically low ratio of sVEGFR-2 þ sVEGFR-3/VEGF-C in the plasma show a circulating pro-lymphangiogenic state during PE; this condition may be a compensatory response to edema and hypertension.…”

Abnormal lymphatic vessel development is associated with decreased decidual regulatory T cells in severe preeclampsia

“…36,37 Among them, VEGF-C and VEGF-D are known to induce lymphangiogenesis through VEGF receptor (VEGFR)-2,3 signaling. 39 Recent studies reported that plasma levels of VEGFR-2, a crucial regulator of lymphangiogenesis, were decreased in preeclamptic women. 39 Recent studies reported that plasma levels of VEGFR-2, a crucial regulator of lymphangiogenesis, were decreased in preeclamptic women.…”

Power Electronic Semiconductor Materials for Automotive and Energy Saving Applications – SiC, GaN, Ga2O3, and Diamond

“…2830°C. [3] Hereby SiC decomposes into carbon and a silicon rich solution of up to 13 at % of carbon. In crystal growth technology SiC boules are mainly grown from the vapor by the so called physical vapor transport (PVT) method ( Figure 2).…”