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Article

Decreased Lymphangiogenic Activities and Genes Expression of Cord Blood Lymphatic Endothelial Progenitor Cells (VEGFR3+/Pod+/CD11b+ Cells) in Patient with Preeclampsia

by 1,2, 1,2, 2,3 and 1,2,*
1
Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University Health System, Seoul 03722, Korea
2
Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul 03722, Korea
3
Program in Biochemistry, Cellular & Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Jolanta Weave, Germano Guerra and Francesco Moccia
Int. J. Mol. Sci. 2021, 22(8), 4237; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084237
Received: 10 March 2021 / Revised: 12 April 2021 / Accepted: 16 April 2021 / Published: 19 April 2021
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
The abnormal development or disruption of the lymphatic vasculature has been implicated in metabolic and hypertensive diseases. Recent evidence suggests that the offspring exposed to preeclampsia (PE) in utero are at higher risk of long-term health problems, such as cardiovascular and metabolic diseases in adulthood, owing to in utero fetal programming. We aimed to investigate lymphangiogenic activities in the lymphatic endothelial progenitor cells (LEPCs) of the offspring of PE. Human umbilical cord blood LEPCs from pregnant women with severe PE (n = 10) and gestationally matched normal pregnancies (n = 10) were purified with anti-vascular endothelial growth factor receptor 3 (VEGFR3)/podoplanin/CD11b microbeads using a magnetic cell sorter device. LEPCs from PE displayed significantly delayed differentiation and reduced formation of lymphatic endothelial cell (LEC) colonies compared with the LEPCs from normal pregnancies. LECs differentiated from PE-derived LEPCs exhibited decreased tube formation, migration, proliferation, adhesion, wound healing, and 3D-sprouting activities as well as increased lymphatic permeability through the disorganization of VE-cadherin junctions, compared with the normal pregnancy-derived LECs. In vivo, LEPCs from PE showed significantly reduced lymphatic vessel formation compared to the LEPCs of the normal pregnancy. Gene expression analysis revealed that compared to the normal pregnancy-derived LECs, the PE-derived LECs showed a significant decrease in the expression of pro-lymphangiogenic genes (GREM1, EPHB3, VEGFA, AMOT, THSD7A, ANGPTL4, SEMA5A, FGF2, and GBX2). Collectively, our findings demonstrate, for the first time, that LEPCs from PE have reduced lymphangiogenic activities in vitro and in vivo and show the decreased expression of pro-lymphangiogenic genes. This study opens a new avenue for investigation of the molecular mechanism of LEPC differentiation and lymphangiogenesis in the offspring of PE and subsequently may impact the treatment of long-term health problems such as cardiovascular and metabolic disorders of offspring with abnormal development of lymphatic vasculature. View Full-Text
Keywords: lymphatic endothelial progenitor cells; lymphangiogenesis; differentiation; preeclampsia lymphatic endothelial progenitor cells; lymphangiogenesis; differentiation; preeclampsia
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MDPI and ACS Style

Kwon, H.; Kwon, J.-Y.; Song, J.; Maeng, Y.-S. Decreased Lymphangiogenic Activities and Genes Expression of Cord Blood Lymphatic Endothelial Progenitor Cells (VEGFR3+/Pod+/CD11b+ Cells) in Patient with Preeclampsia. Int. J. Mol. Sci. 2021, 22, 4237. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084237

AMA Style

Kwon H, Kwon J-Y, Song J, Maeng Y-S. Decreased Lymphangiogenic Activities and Genes Expression of Cord Blood Lymphatic Endothelial Progenitor Cells (VEGFR3+/Pod+/CD11b+ Cells) in Patient with Preeclampsia. International Journal of Molecular Sciences. 2021; 22(8):4237. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084237

Chicago/Turabian Style

Kwon, Hayan, Ja-Young Kwon, Jeeun Song, and Yong-Sun Maeng. 2021. "Decreased Lymphangiogenic Activities and Genes Expression of Cord Blood Lymphatic Endothelial Progenitor Cells (VEGFR3+/Pod+/CD11b+ Cells) in Patient with Preeclampsia" International Journal of Molecular Sciences 22, no. 8: 4237. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084237

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