Molecular Characterization of EG-VEGF-mediated Angiogenesis: Differential Effects on Microvascular and Macrovascular Endothelial Cells

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2010 Jul 1

PMID 20587779

Citations 34

Authors

Sophie Brouillet

Pascale Hoffmann

Mohamed Benharouga

Aude Salomon

Jean-Patrick Schaal

Jean-Jacques Feige

Nadia Alfaidy

Affiliations

Soon will be listed here.

Abstract

Endocrine gland derived vascular endothelial growth factor (EG-VEGF) also called prokineticin (PK1), has been identified and linked to several biological processes including angiogenesis. EG-VEGF is abundantly expressed in the highest vascularized organ, the human placenta. Here we characterized its angiogenic effect using different experimental procedures. Immunohistochemistry was used to localize EG-VEGF receptors (PROKR1 and PROKR2) in placental and umbilical cord tissue. Primary microvascular placental endothelial cell (HPEC) and umbilical vein-derived macrovascular EC (HUVEC) were used to assess its effects on proliferation, migration, cell survival, pseudovascular organization, spheroid sprouting, permeability and paracellular transport. siRNA and neutralizing antibody strategies were used to differentiate PROKR1- from PROKR2-mediated effects. Our results show that 1) HPEC and HUVEC express both types of receptors 2) EG-VEGF stimulates HPEC's proliferation, migration and survival, but increases only survival in HUVECs. and 3) EG-VEGF was more potent than VEGF in stimulating HPEC sprout formation, pseudovascular organization, and it significantly increases HPEC permeability and paracellular transport. More importantly, we demonstrated that PROKR1 mediates EG-VEGF angiogenic effects, whereas PROKR2 mediates cellular permeability. Altogether, these data characterized angiogenic processes mediated by EG-VEGF, depicted a new angiogenic factor in the placenta, and suggest a novel view of the regulation of angiogenesis in placental pathologies.

Citing Articles

Antagonisation of Prokineticin Receptor-2 Attenuates Preeclampsia Symptoms.

Sergent F, Vaiman D, Raia-Barjat T, Younes H, Marquette C, Desseux M J Cell Mol Med. 2025; 29(2):e70346.

PMID: 39817714 PMC: 11736873. DOI: 10.1111/jcmm.70346.

An Endothelial Cell Is Not Simply an Endothelial Cell.

Limbu S, McCloskey K Stem Cells Dev. 2024; 33(19-20):517-527.

PMID: 39030822 PMC: 11564855. DOI: 10.1089/scd.2024.0088.

Unveiling the Role of Tryptophan 2,3-Dioxygenase in the Angiogenic Process.

Cecchi M, Anceschi C, Silvano A, Coniglio M, Chinnici A, Magnelli L Pharmaceuticals (Basel). 2024; 17(5).

PMID: 38794128 PMC: 11124529. DOI: 10.3390/ph17050558.

Novel Insights into Prokineticin 1 Role in Pregnancy-related Diseases.

Cheng X, Li M, Peng T Int J Med Sci. 2024; 21(1):27-36.

PMID: 38164347 PMC: 10750342. DOI: 10.7150/ijms.76817.

RGD-Based Fluorescence to Assess Placental Angiogenesis.

Josserand V, Lavaud J, Keramidas M, Collet C, Traboulsi W, Hoffmann P Methods Mol Biol. 2023; 2728:131-136.

PMID: 38019397 DOI: 10.1007/978-1-0716-3495-0_11.

References

Kisliouk T, Levy N, Hurwitz A, Meidan R . Presence and regulation of endocrine gland vascular endothelial growth factor/prokineticin-1 and its receptors in ovarian cells. J Clin Endocrinol Metab. 2003; 88(8):3700-7. DOI: 10.1210/jc.2003-030492. View

Dellian M, Witwer B, Salehi H, Yuan F, Jain R . Quantitation and physiological characterization of angiogenic vessels in mice: effect of basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and host microenvironment. Am J Pathol. 1996; 149(1):59-71. PMC: 1865247. View

Ngan E, Shum C, Poon H, Sham M, Garcia-Barcelo M, Lui V . Prokineticin-1 (Prok-1) works coordinately with glial cell line-derived neurotrophic factor (GDNF) to mediate proliferation and differentiation of enteric neural crest cells. Biochim Biophys Acta. 2007; 1783(3):467-78. DOI: 10.1016/j.bbamcr.2007.09.005. View

Murray J . On the mechanochemical theory of biological pattern formation with application to vasculogenesis. C R Biol. 2003; 326(2):239-52. DOI: 10.1016/s1631-0691(03)00065-9. View

Demir R, Kayisli U, Seval Y, Celik-Ozenci C, Korgun E, Demir-Weusten A . Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: differences between placental vasculogenesis and angiogenesis. Placenta. 2004; 25(6):560-72. DOI: 10.1016/j.placenta.2003.11.011. View

Gallery E, Rowe J, Schrieber L, Jackson C . Isolation and purification of microvascular endothelium from human decidual tissue in the late phase of pregnancy. Am J Obstet Gynecol. 1991; 165(1):191-6. DOI: 10.1016/0002-9378(91)90249-q. View

Metz J, Heinrich D, Forssmann W . Gap junctions in hemodichorial and hemotrichorial placentae. Cell Tissue Res. 1976; 171(3):305-15. DOI: 10.1007/BF00224656. View

Lin R, LeCouter J, Kowalski J, Ferrara N . Characterization of endocrine gland-derived vascular endothelial growth factor signaling in adrenal cortex capillary endothelial cells. J Biol Chem. 2001; 277(10):8724-9. DOI: 10.1074/jbc.M110594200. View

Lang I, Pabst M, Hiden U, Blaschitz A, Dohr G, Hahn T . Heterogeneity of microvascular endothelial cells isolated from human term placenta and macrovascular umbilical vein endothelial cells. Eur J Cell Biol. 2003; 82(4):163-73. DOI: 10.1078/0171-9335-00306. View

10.

Stewart P, Wiley M . Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail--chick transplantation chimeras. Dev Biol. 1981; 84(1):183-92. DOI: 10.1016/0012-1606(81)90382-1. View

11.

Risau W . Mechanisms of angiogenesis. Nature. 1997; 386(6626):671-4. DOI: 10.1038/386671a0. View

12.

Lin D, Bullock C, Ehlert F, Chen J, Tian H, Zhou Q . Identification and molecular characterization of two closely related G protein-coupled receptors activated by prokineticins/endocrine gland vascular endothelial growth factor. J Biol Chem. 2002; 277(22):19276-80. DOI: 10.1074/jbc.M202139200. View

13.

Urayama K, Dedeoglu D, Guilini C, Frantz S, Ertl G, Messaddeq N . Transgenic myocardial overexpression of prokineticin receptor-2 (GPR73b) induces hypertrophy and capillary vessel leakage. Cardiovasc Res. 2008; 81(1):28-37. DOI: 10.1093/cvr/cvn251. View

14.

Charnock-Jones D, Kaufmann P, Mayhew T . Aspects of human fetoplacental vasculogenesis and angiogenesis. I. Molecular regulation. Placenta. 2004; 25(2-3):103-13. DOI: 10.1016/j.placenta.2003.10.004. View

15.

Urayama K, Guilini C, Turkeri G, Takir S, Kurose H, Messaddeq N . Prokineticin receptor-1 induces neovascularization and epicardial-derived progenitor cell differentiation. Arterioscler Thromb Vasc Biol. 2008; 28(5):841-9. DOI: 10.1161/ATVBAHA.108.162404. View

16.

Burton G, Jauniaux E . Sonographic, stereological and Doppler flow velocimetric assessments of placental maturity. Br J Obstet Gynaecol. 1995; 102(10):818-25. DOI: 10.1111/j.1471-0528.1995.tb10849.x. View

17.

Hebert C, Luscinskas F, Kiely J, Luis E, Darbonne W, Bennett G . Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. J Immunol. 1990; 145(9):3033-40. View

18.

Jinga V, Gafencu A, Antohe F, Constantinescu E, Heltianu C, Raicu M . Establishment of a pure vascular endothelial cell line from human placenta. Placenta. 2000; 21(4):325-36. DOI: 10.1053/plac.1999.0492. View

19.

ROBERTS W, Delaat J, Nagane M, Huang S, Cavenee W, Palade G . Host microvasculature influence on tumor vascular morphology and endothelial gene expression. Am J Pathol. 1998; 153(4):1239-48. PMC: 1853053. DOI: 10.1016/S0002-9440(10)65668-4. View

20.

Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z . Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999; 13(1):9-22. View