Correlation between Vasoinhibin and CathepsinD Serum Levels in Pregnancy Induced Hypertension Syndrome Patients

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 112-141-Hypothalamus-Pituitary Development & Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-136
Ryojun Nakajima*1, Asuka Hirota1, Tsukasa Watanabe1, Eri Nakamura1, Naoya Ikoma1, Chizuko Kamiya2, Tomoaki Ikeda3, Michiyo Ishida1 and Toshio Harigaya1
1Meiji University, Kawasaki Kanagawa, Japan, 2National Cerebral and Cardiovascular Center, Suita Osaka, Japan, 3Mie University, Tsu Mie, Japan
Prolactin (PRL) has been well known to have several post-translational modification variants. As one of these variants, N-terminal cleaved PRL by cathepsinD (CathD), has antagonistic action against native PRL. Furthermore, N-terminal cleaved variants larger than 11kDa derived from GH/PRL family are named vasoinhibins (Vi) that have anti-angiogenic and pro-apoptotic properties. Vi has been reported to have relation with several diseases including in pregnancy induced hypertension (PIH).

 PIH, a disease associated with pregnancy and characterized by transient high blood pressure, is categorized into gestational hypertension, preeclampsia, superimposed preeclampsia and eclampsia. Vi was detected from urine and amnion liquid in preeclampsia. In order to clarify pathogenic mechanisms of PIH, we tried to detect Vi amount and CathD activity in PIH patient’s serum and to determine the relationship between these factors and the disease. Serum samples were obtained from 5 patients with preeclampsia, 1 with superimposed preeclampsia, and 1 with gestational hypertension. We also obtained samples from 4 healthy pregnant women as control. Bloods were collected at a month before delivery, the first day after delivery and a month after delivery. All women were provided a written informed consent before collection of samples. Vi derived from PRL in serum was determined using immunoprecipitation with anti-PRL antibody and capillary electrophoresis. CathD activity in serum was determined by the amount of cleavage product from specific substrate. Correlations between Vi amounts and CathD activities were analyzed by Pearson product-moment correlation coefficient.

 Vi amounts at a month before delivery and the first day after delivery in patients with PIH were significantly higher than those in normal controls. Furthermore, despite almost normalized blood pressure in patients with PIH , Vi amounts at a month after delivery in all patients with PIH were significantly higher those in normal controls (0.45 ± 0.16Fu vs. 6.90 ± 1.94Fu). Similarly, CathD activities at every determined period in all patients with PIH were higher than those in normal controls. Vi amounts and CathD activities had significantly positive correlation with PIH.

These results suggest that Vi may relate the occurrence of PIH. Although several enzymes, such as matrix metalloproteinase family, are known to produce Vi from GH/PRL family, this study suggests that CathD can cleave PRL into Vi among patients with PIH. It is difficult to predict the occurrence of PIH in pregnant women. We need further investigations to know whether Vi and CathD are useful marker for early detection of PIH.

Nothing to Disclose: RN, AH, TW, EN, NI, CK, TI, MI, TH

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