Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associatedwith pre-eclampsia
Abstract
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.
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This finding is consistent with a role for CCN1 in placental angiogenesis and decidual tissue remodeling, and evidence suggests serum CCN1 levels may serve as a marker for early diagnosis of pre-eclampsia.
“This finding is consistent with a role for CCN1 in placental angiogenesis and decidual tissue remodeling, and evidence suggests that serum levels of CCN1 may serve as a marker for early diagnosis of pre-eclampsia [96].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [95]
CCN1 expression is greatly decreased in placentae associated with pre-eclampsia.
“CCN1 expression is greatly decreased in placentae associated with pre-eclampsia, a condition thought to result from a shallow invasion of the extravillous trophoblast into the decidua, followed by incomplete remodeling of the maternal vascular structures [95].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [95]
In the human placenta, CCN1 is most highly expressed in the second and third trimesters, especially in non-proliferating interstitial extravillous trophoblastic giant cells, vascular endothelial cells, and mesenchymal and stromal cells of placental villi.
“In the human placenta, CCN1 is most highly expressed in the second and third trimesters of pregnancy, especially in non-proliferating interstitial extravillous trophoblastic giant cells, vascular endothelial cells, and mesenchymal and stromal cells of the placental villi [95].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [95]
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- Authors
- Gellhaus, A.
- Affiliations
- Essen University Hospital (DE)
- Corresponding author
- Gellhaus, A.
- ORCID
- Gellhaus, A.
- Venue
- Molecular Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-04-26
- Volume
- 12
- Issue
- 6
- Pages
- 389-399
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- OpenAlex
- W2122044798
- Cited by
- 72
- References
- 50
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 7
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (5r01hd042558-03)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD42558-01)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- preeclampsia, CYR61, NOV, CCN3, CCN family, human placenta, extravillous trophoblast, trophoblast giant cells, placental angiogenesis, HELLP syndrome, placental insufficiency, trophoblast invasion
- MeSH terms
- Adult, Female, Humans, Immunohistochemistry, Microscopy, Fluorescence, Placenta, Pre-Eclampsia, Pregnancy, RNA, Messenger, Blotting, Western, HELLP Syndrome, Immediate-Early Proteins, Reverse Transcriptase Polymerase Chain Reaction, Intercellular Signaling Peptides and Proteins, Connective Tissue Growth Factor, Nephroblastoma Overexpressed Protein, Cysteine-Rich Protein 61
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