Decreased expression of apelin in placentas from severe pre-eclampsia patients

Inuzuka, H.; Nishizawa, Haruki; Inagaki, Asako; Suzuki, Manami; Ota, Sayuri; Miyamura, Hironori; Miyazaki, Junichi; Sekiya, Takao; Kurahashi, Hiroki; Udagawa, Yasuhiro

doi:10.3109/10641955.2013.813535

Cited by 49 publications

(48 citation statements)

References 40 publications

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“…Apelin exhibits a hypotensive effect through an endothelium and nitric oxide-dependent mechanism, with lower levels observed in patients with hypertension (35). Our data are the first to report that apelin expression in the maternal endothelium in PE is decreased and follows the same pattern of decreased expression in the placenta (18). Additionally, we observed a decrease in prostacyclin synthase expression, which suggests decreased prostacyclin production and supports previous data of decreased circulating prostacyclin levels in PE (8).…”

Section: A T 1 R E T a R E T B Rsupporting

confidence: 79%

Microvascular endothelial cells from preeclamptic women exhibit altered expression of angiogenic and vasopressor factors

Lee

Nevo

2016

American Journal of Physiology-Heart and Circulatory Physiology

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Section: A T 1 R E T a R E T B Rsupporting

confidence: 79%

Microvascular endothelial cells from preeclamptic women exhibit altered expression of angiogenic and vasopressor factors

Lee

Nevo

2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…Plasma apelin measured at delivery was reported to be lower (6), not different (29), or higher (20) in women with preeclampsia compared with women with normal pregnancy. It is known that apelin levels are influenced by endogenous enzyme inhibitors that are present in the plasma (58).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have recently investigated the expression of apelin in human placenta. Inzukua et al (20) reported that apelin mRNA and immunohistochemical peptide levels were lower in placentas from preeclamptic women. Our findings agree with this study and demonstrate that total apelin content in the chorionic villi is 30% lower in preeclamptic women as quantified by direct RIA.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of apelin in the human placental chorionic villi from preeclamptic pregnancies

Yamaleyeva

Chappell

Brosnihan

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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The role of the endogenous apelin system in pregnancy is not well understood. Apelin's actions in pregnancy are further complicated by the expression of multiple forms of the peptide. Using radioimmunoassay (RIA) alone, we established the expression of apelin content in the chorionic villi of preeclamptic (PRE) and normal pregnant women (NORM) at 36 -38 wk of gestation. Total apelin content was lower in PRE compared with NORM chorionic villi (49.7 Ϯ 3.4 vs. 72.3 Ϯ 9.8 fmol/mg protein; n ϭ 20 -22) and was associated with a trend for lower preproapelin mRNA in the PRE. Further characterization of apelin isoforms by HPLC-RIA was conducted in pooled samples from each group. The expression patterns of apelin peptides in NORM and PRE villi revealed little or no apelin-36 or apelin-17. Pyroglutamate apelin-13 [(Pyr 1 )-apelin-13] was the predominant form of the peptide in NORM and PRE villi. Angiotensin-converting enzyme 2 (ACE2) activity was higher in PRE villi (572.0 Ϯ 23.0 vs. 485.3 Ϯ 24.8 pmol·mg Ϫ1 ·min Ϫ1 ; n ϭ 18 -22). A low dose of ANG II (1 nM; 2 h) decreased apelin release in NORM villous explants that was blocked by the ANG II receptor 1 (AT1) antagonist losartan. Moreover, losartan enhanced apelin release above the 2-h baseline levels in both NORM and PRE villi (P Ͻ 0.05). In summary, these studies are the first to demonstrate the lower apelin content in human placental chorionic villi of PRE subjects using quantitative RIA. (Pyr 1 )-apelin-13 is the predominant form of endogenous apelin in the chorionic villi of NORM and PRE. The potential mechanism of lower apelin expression in the PRE villi may involve a negative regulation of apelin by ANG II. apelin-13; apelin receptor; ACE2; pregnancy; explant PREECLAMPSIA IS A pregnancy-induced hypertensive disorder that occurs in 5-7% of all pregnancies worldwide (54). It is associated with maternal perinatal morbidity and mortality and a high risk of premature birth and fetal growth restriction. Despite continued research, the pathogenesis of preeclampsia is still unknown. The endogenous apelin system is an emerging target for the regulation of cardiovascular homeostasis (22); however, its role in pregnancy is not well understood. The levels of preproapelin mRNA are widespread in human tissues, and high levels were identified in the placenta (38), suggesting a possible placental origin of apelin in pregnancy. Apelin may have a paracrine role in human chorionic villi as it has been identified in cytotrophoblasts, in syncytiotrophoblasts, and in fetal endothelial cells (13,15). A positive correlation between maternal and fetal plasma apelin was observed in full-term normal pregnancies (37). Moreover, a transplacental transfer of apelin with potential impact on fetal growth was suggested (37). Apelin is a ligand for the human G protein-coupled receptor APJ (40). The role of APJ in embryonic development was shown by the existence of cardiovascular developmental defects in APJ-deficient mice (11). In addition, a small litter size and a significant loss of homozygous ani...

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“…Studies have shown that apelin is also closely associated with normal pregnancies and pre-eclampsia. Compared with normal pregnancies, the RNA and protein level of apelin are significantly decreased in pre-eclamptic placentas (79,80). The above findings suggest that the reduced expression of apelin may be associated with preeclampsia and the apelinergic system plays an important role in preeclampsia-induced hypertensive maternal disorders.…”

Section: Apelin Inhibits Hypertension In Pre-eclampsia By Regulating mentioning

confidence: 57%

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

Zhou

Cao

Chen

2016

International Journal of Molecular Medicine

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Abstract. Apelin, the endogenous ligand of APJ which is a member of G protein-coupled receptors, has been shown to be expressed in a variety of tissues in vivo and to exert significant biological effects. Studies have indicated that the apelin/APJ system is involved in the regulation of a variety of physiological functions and pathological processes, and that it is associated with cardiovascular diseases (such as atherosclerosis, hypertension, heart failure and myocardial injury), diabetes with microvascular complications, ischemia reperfusion injury, tumors, pre-eclampsia, as well as others. The occurrence of these diseases is closely related to endothelial dysfunction and the local inflammatory response; however, the occurrence of oxidative stress is related to vascular injury, due to the excessive generation of reactive oxygen species (ROS) and can lead to vascular damage and a series of inflammatory reactions. Therefore, this review summarizes the association between apelin/APJ, oxidative stress and inflammation-related diseases. In addition, drugs targeting the apelin/APJ system are recommended, thus providing a novel therapeutic strategy for oxidative stress-related inflammatory diseases.

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Decreased expression of apelin in placentas from severe pre-eclampsia patients

Abstract: A functional role of the apelin--APJ system is likely in early gestation, and this raises the possibility that a dysfunctional apelin--APJ system contributes to the onset of pre-eclampsia via decreased angiogenic activity in placental implantation.

Cited by 49 publications

References 40 publications

Microvascular endothelial cells from preeclamptic women exhibit altered expression of angiogenic and vasopressor factors

Microvascular endothelial cells from preeclamptic women exhibit altered expression of angiogenic and vasopressor factors

Downregulation of apelin in the human placental chorionic villi from preeclamptic pregnancies

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

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