子痫前期患者循环中的淋巴管生成因子
Circulating lymphangiogenic factors in preeclampsia.
作者信息
Lely A Titia, Salahuddin Saira, Holwerda Kim M, Karumanchi S Ananth, Rana Sarosh
机构信息
Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1,Groningen, The Netherlands.
出版信息
Hypertens Pregnancy. 2013;32(1):42-9. doi: 10.3109/10641955.2012.697953. Epub 2012 Sep 7.
BACKGROUND
Preeclampsia (PE), 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 PE has not been investigated. Recently, impaired vascular endothelial growth factor C (VEGF-C) (factor that regulates lymphangiogenesis) signaling 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 PE 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), PE (n = 20), and normotensive pregnancies (NP, n = 20) in the third trimester and values were reported as mean ± SD in pg/mL.
RESULTS
As previously reported, sVEGFR-1 levels were significantly higher in subjects with PE (19,938 ± 12,973) 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 toward 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.
CONCLUSIONS
PE 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 suggest that the circulating pro-lymphangiogenic state during PE may be a compensatory response to edema and hypertension. Additional studies are needed to evaluate the clinical relevance of the altered lymphangiogenic signaling pathway during PE.
背景
子痫前期（PE）是一种人类妊娠特有的疾病，其特征是由于循环中高水平的可溶性血管内皮生长因子1（sVEGFR-1）导致的抗血管生成状态。然而，淋巴管生成在PE中的作用尚未得到研究。最近，血管内皮生长因子C（VEGF-C，一种调节淋巴管生成的因子）信号受损与间质性水肿和盐敏感性高血压的发病机制有关。因此，我们推测循环中的VEGF-C及其循环受体（sVEGFR-2和sVEGFR-3）在PE中也可能发生改变，并与该疾病表型的严重程度相关。
方法
我们分析了妊娠晚期患有妊娠期高血压（GHTN，n = 20）、PE（n = 20）和血压正常的孕妇（NP，n = 20）血浆中VEGF-C、sVEGFR-1、sVEGFR-2和sVEGFR-3的水平，结果以pg/mL为单位表示为平均值±标准差。
结果
如先前报道，PE患者（19,938 ± 12,973）的sVEGFR-1水平显著高于GHTN患者（7156 ± 5432），p < 0.01，或高于NP患者（7760 ± 6018），p < 0.01。GHTN患者（676 ± 323）的VEGF-C水平低于PE患者（1335 ± 625），p < 0.01，但与NP患者（971 ± 556）相比无统计学差异，p = 0.11。与GHTN或NP相比，PE患者的sVEGFR-2有降低趋势。有趣的是，与NP患者（83,709 ± 24,983）相比，PE患者的sVEGFR-3显著降低（54,371 ± 21,107），p < 0.01，但与GHTN患者（54,642 ± 26,947）相比无差异。与GHTN患者（113 ± 72），p < 0.01或NP患者（133 ± 91），p < 0.01相比，PE患者中sVEGFR-2 + sVEGFR-3/VEGF-C的比值显著降低（57 ± 38）。
结论
PE的特征是循环中促淋巴管生成状态，表现为sVEGFR-3降低、sVEGFR-2略有降低、VEGF-C升高以及sVEGFR-2 + sVEGFR-3/VEGF-C的比值显著降低。我们的数据表明，PE期间循环中的促淋巴管生成状态可能是对水肿和高血压的一种代偿反应。需要进一步研究来评估PE期间淋巴管生成信号通路改变的临床相关性。
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