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

Am J Physiol Endocrinol Metab. 2015 Nov 15;309(10):E852-60. doi: 10.1152/ajpendo.00272.2015. Epub 2015 Sep 22.


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±3.4 vs. 72.3±9.8 fmol/mg protein; n=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 [(Pyr1)-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±23.0 vs. 485.3±24.8 pmol·mg(-1)·min(-1); n=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<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. (Pyr1)-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.

Keywords: ACE2; apelin receptor; apelin-13; explant; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin II / chemistry
  • Angiotensin II / metabolism
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme 2
  • Apelin
  • Chorionic Villi / drug effects
  • Chorionic Villi / metabolism*
  • Chorionic Villi / pathology
  • Down-Regulation* / drug effects
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Peptidyl-Dipeptidase A / metabolism
  • Pre-Eclampsia / drug therapy
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Pregnancy Trimester, Third
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Protein Processing, Post-Translational / drug effects
  • Pyrrolidonecarboxylic Acid / metabolism
  • RNA, Messenger / metabolism
  • Tissue Culture Techniques
  • Young Adult


  • APLN protein, human
  • Angiotensin II Type 1 Receptor Blockers
  • Apelin
  • Intercellular Signaling Peptides and Proteins
  • Protein Isoforms
  • Protein Precursors
  • RNA, Messenger
  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Pyrrolidonecarboxylic Acid