OS064. Contribute of the L-cysteine/ H2S pathway in placenta homeostasisin hypertensive disorders

L Sarno; G Mattace Raso; R D'Emmanuele di Villa Bianca; E Mitidieri; G M Maruotti; G Esposito; R Meli; R Sorrentino; P Martinelli

doi:10.1016/j.preghy.2012.04.065

OS064. Contribute of the L-cysteine/ H2S pathway in placenta homeostasisin hypertensive disorders

Pregnancy Hypertens. 2012 Jul;2(3):211-2. doi: 10.1016/j.preghy.2012.04.065. Epub 2012 Jun 13.

Authors

L Sarno¹, G Mattace Raso², R D'Emmanuele di Villa Bianca², E Mitidieri², G M Maruotti¹, G Esposito¹, R Meli², R Sorrentino², P Martinelli¹

Affiliations

¹ Obstetrics & Gynecology - High Risk Pregnancy Unit, University Federico II, Naples, Italy.
² Department of Experimental Pharmacology, University Federico II, Naples, Italy.

PMID: 26105277
DOI: 10.1016/j.preghy.2012.04.065

Abstract

Introduction: Hydrogen sulfide (H2S) is considered the third endogenous gas transmitter besides nitric oxide and carbon monoxide [1]. It is produced from L-cysteine or L-methionine via the enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). H2S is involved in the control of vascular homeostasis, having either relaxant or contractant effect on smooth muscle cells. The H2S involvement in rat and human intrauterine tissues has also been shown [2].

Objectives: The aim of our study was to investigate the L-cysteine/ H2S pathway in rat and human placenta in hypertensive state.

Methods: Placental samples were collected from spontaneous hypertensive rats (SHR) and normotensive rat (Wistar Kyoto; WKY). In parallel, placental samples were collected from 10 pre-eclamptic women and 5 controls after caesarean sections. Pre-eclamptic women were divided into two subgroups: Group1 (women who developed Early Preeclampsia, n=4); Group2 (women who developed Late Preeclampsia, n=6). The expression of CBS and CSE was evaluated in sample tissues by Western blotting analysis. The enzymatic activity was assessed in basal and stimulated (L- cysteine) condiction by a colorimetric assay. Statistical analysis was performed by using Student's t test. P<0,05 was considered as statistically significant.

Results: The expression of CBS and CSE in placenta of SHR rats were significantly reduced (p<0.05) compared to WKY. The H2S production resulted significantly (p<0,05) lower in SHR than WKY rats. In human placenta, the basal H2S production was similar in the three groups; interestingly the H2S production by adding L-cysteine, was higher in Late Preeclampsia compared to control group.

Conclusion: H2S was produced in rat and human placenta. CBS and CSE, the enzymes involved in the production of H2S, were down-regulated in SHR rats and, as a consequence the H2S production was significantly reduced. Starting from these data, we tried to analyze the role of hydrogen sulfide in preeclampsia to assess the contribute of this gas transmitter in the development of this condition. Unexpectedly, preliminary data demonstrated that in women developing Late Preeclampsia there was an higher production of H2S after stimulation with L-cysteine, not revealed in Early Preeclampsia or in healthy control group. Our results indicated that the L-cysteine/H2S pathway could contribute to the development of preeclampsia condition.