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Pituitary Hormones Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Prolactin (PRL) Modulate Endothelial Colony Forming Cells Angiogenic and Thrombotic Properties

1Université de Paris, Innovative Therapies in Haemostasis INSERM S 1140, Paris, France, 2Normandie Univ, UNIROUEN, Rouen University Hospital, INSERM U 1096, Rouen, France, 3Université de Paris, Innovative Therapies in Haemostasis INSERM S 1140, Hematology Department and Biosurgical Research Lab, Georges Pompidou European Hospital, Paris, France, 4University of Louisville School of Medicine, Stem Cell Institute at James Graham Brown Cancer Center, Louisville, United States, 5Faculté de Médecine, Université de Paris, INSERM, UMR S 970, Cardiovascular Research Center, Service de Médecine Vasculaire, Hôpital Européen Georges-Pompidou, APHP Centre, Paris, France

Abstract Number: PB2034

Meeting: ISTH 2020 Congress

Theme: Vascular Biology » Stem Cells and Vascular Cell Growth

Background: Pituitary sexual hormones (SexHs) follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) have been described to stimulate mobilization, migration or proliferation of several human hematopoietic, stem or cancer cells. Endothelial colony forming cells (ECFCs) have been identified as the human postnatal vasculogenic cells involved in vascular repair and thrombotic disorders.

Aims: Our aim was to determine how FSH, LH and PRL could contribute to ECFC commitment and modulate their angiogenic properties.

Methods: We investigated effect of SexHs on angiogenic properties and prothrombotic in ECFCs derived from cord blood.

Results: We showed that FSH, LH and PRL at the dose of 100ng/mL did not modify ECFC commitment from mononuclear cells. They were all CD31+ CD45- CD90- with a strict endothelial phenotype. However, FSH, LH and PRL significantly increased ECFC migration, by Transwell chemotaxis assay and wound healing assays without affecting proliferation properties. We showed also that hormones gave more sprouts than control in a three-dimensional fibrin gel assays with ECFC seeded onto Cytodex® 3 microcarrier beads and embedded in fibrin gel containing SexHs . Moreover, we observed an increase in pro thrombotic properties in vitro by measuring thrombin generation time (TGT) of poor platelet plasma with ECFCs pretreated with SexHs during 72 hours. LH and PRL pretreatment of ECFCs increased total thrombin formation measured by endogenous thrombin potential (ETP) and maximal peak. This effect was associated with a decreased expression of the median fluorescence index of the endothelial protein C receptor treated with LH and PRL ECFC. The thrombomodulin expression was not affected.

Conclusions: This study provides new evidence that SexHs improves angiogenic potential of ECFCs and their procoagulant status by modulating EPCR. Our data also emphasize potential endothelial dysfunction associated with thrombosis recurrence induced by SexHs.

To cite this abstract in AMA style:

Detriche G, Billoir P, Gendron N, Rossi E, Guerin CL, Lokajczyk A, Kucia M, Ratajczak MZ, Mirault T, Smadja D. Pituitary Hormones Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Prolactin (PRL) Modulate Endothelial Colony Forming Cells Angiogenic and Thrombotic Properties [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/pituitary-hormones-follicle-stimulating-hormone-fsh-luteinizing-hormone-lh-and-prolactin-prl-modulate-endothelial-colony-forming-cells-angiogenic-and-thrombotic-properties/. Accessed January 27, 2022.

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