Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associated with pre-eclampsia

Mol Hum Reprod. 2006 Jun;12(6):389-99. doi: 10.1093/molehr/gal044. Epub 2006 May 4.


The pregnancy disorder pre-eclampsia (PE) is thought to be caused in part by shallow invasion of the extravillous trophoblast (EVT) leading to uteroplacental insufficiency and hypoxia. Here, we focused on the expressions of cysteine-rich 61 (CYR61, CCN1) and nephroblastoma overexpressed (NOV, CCN3), members of the CCN family of angiogenic regulators, in human placenta during normal pregnancy compared with pre-eclamptic and HELLP placentae using quantitative RT-PCR, western blotting and immunocytochemistry. During normal pregnancy, both proteins showed increasing expression levels and were strongly coexpressed in endothelial cells of vessels, stromal cells and interstitial EVT giant cells. However, NOV showed an earlier onset of expression in villous endothelial cells during gestation compared with CYR61, which may signify distinct roles of these proteins in placental angiogenesis. In early-onset pre-eclamptic placentae, both CYR61 and NOV were expressed at a significantly lower level compared with normal matched controls. This decrease of CYR61 and NOV in pre-eclamptic placentae is not associated with a decrease of the endothelial marker CD34 or vimentin. No obvious changes in the localization of CYR61 and NOV in pre-eclamptic placentae were detected but a change in the intracellular distribution in trophoblast giant cells. Our data point to a potential role of both molecules in the pathogenesis of early-onset PE.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Western
  • Connective Tissue Growth Factor
  • Cysteine-Rich Protein 61
  • Female
  • HELLP Syndrome / genetics
  • HELLP Syndrome / metabolism
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Microscopy, Fluorescence
  • Nephroblastoma Overexpressed Protein
  • Placenta / metabolism
  • Placenta / pathology
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • CCN1 protein, human
  • CCN2 protein, human
  • CCN3 protein, human
  • Cysteine-Rich Protein 61
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Nephroblastoma Overexpressed Protein
  • RNA, Messenger
  • Connective Tissue Growth Factor