title: Expression of angiotensin II receptor-like 1 in the placentas of pregnancy-induced hypertension.
abstract: Angiotensin II receptor-like 1 (APJ), a G protein-coupled receptor that was identified as a homologue of angiotensin II type 1 (AT1) receptor, exerts antagonistic effects on AT1-mediated vasoconstriction. Studies on pregnancy-induced hypertension (PIH) revealed aberrant activation of AT1 downstream signaling. In contrast, little is known about APJ in the pathophysiology of human pregnancy. In this study, we investigated APJ expression in normal human and PIH placentas. mRNAs were extracted from 50 placental villous tissues of 18 cases with severe PIH (8 late-onset, 4 early-onset, and 6 superimposed PIH) and 32 control pregnancies (including 6 preterm cases). Histopathologic studies were conducted using paraffin-embedded placental tissues from 12 control placentas (from 23 to 39 wk) and 23 PIH placentas (from 24 to 41 wk). Reverse transcriptase-polymerase chain reaction showed that APJ was cooperatively expressed with its ligand apelin and AT1 in controls and in late-onset PIH placentas but was significantly downregulated in early-onset PIH placentas with poor fetal growth. Quantitative reverse transcriptase-polymerase chain reaction analysis revealed upregulated APJ in late-onset PIH placentas but significantly downregulated APJ in early-onset PIH. In immunohistochemical staining, APJ was detected strongly in villous capillary endothelial cells and trophoblasts of late-onset PIH placentas. In contrast, APJ was poorly stained in endothelial cells of hypoplastic villi of early-onset PIH placentas. Collective data indicate that the apelin-APJ system is involved in fetoplacental circulation during human pregnancy. Impaired APJ expression in early-onset PIH placentas may reflect an aggravated placental condition with poor fetal growth.
authors.affiliation: Departments of Molecular Pathology, Yokohama City University Graduate School of Medicine, Japan. mfuruya@yokohama-cu.ac.jp
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Furuya
authors.forename: Mika
authors.initials: M
authors.lastname: Okuda
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Usui
authors.forename: Toshinao
authors.initials: T
authors.lastname: Takenouchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kami
authors.forename: Akinori
authors.initials: A
authors.lastname: Nozawa
authors.forename: Makio
authors.initials: M
authors.lastname: Shozu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Takahashi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
mesh_terms: D000073861:Apelin; D000075244:Apelin Receptors; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled