Gonadotropins as novel active partners in vascular diseases: Insight from angiogenic properties and thrombotic potential of endothelial colony-forming cells.

angiogenesis modulators endothelial colony-forming cells endothelial progenitor cells gonadotropins thrombosis

Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
01 2022
Historique:
received: 17 07 2021
accepted: 06 10 2021
pubmed: 9 10 2021
medline: 11 3 2022
entrez: 8 10 2021
Statut: ppublish

Résumé

The impact of estrogen and testosterone on atherosclerotic cardiovascular disease is well known, but the role of the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) to some extent remain less studied. To explore the angiogenic potential of gonadotropins on endothelial colony-forming cells (ECFCs). We examined the effects of various doses of gonadotropins on ECFCs obtained from cord blood by assessing colony number, proliferation, migration, and sprouting ability. Moreover, we studied thrombin generation in ECFCs exposed to gonadotropins by performing a thrombin generation assay. Finally, we determined the levels of circulating gonadotropins in 30 men, to exclude the effect of estrogen, with lower extremity arterial disease (LEAD), in comparison with age- and sex-matched controls. Exposure to FSH, LH, or PRL resulted in an increase in ECFC migration but showed no effect on proliferation or ECFC commitment from cord blood mononuclear cells. Using a three-dimensional fibrin gel assay, we showed that ECFC sprouting was significantly enhanced by gonadotropins. Exposure to FSH also increased the thrombin generation of ECFCs exposed to FSH. Finally, FSH and LH levels in men with LEAD were higher than those in controls. Gonadotropins increase ECFC-related angiogenesis and may be involved in thrombin generation in cardiovascular disease. Gonadotropins may act as biomarkers; moreover, we hypothesize that gonadotropin-blocking strategies may be a novel interesting therapeutic approach in atherosclerotic cardiovascular disease.

Sections du résumé

BACKGROUND
The impact of estrogen and testosterone on atherosclerotic cardiovascular disease is well known, but the role of the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) to some extent remain less studied.
OBJECTIVES
To explore the angiogenic potential of gonadotropins on endothelial colony-forming cells (ECFCs).
METHODS
We examined the effects of various doses of gonadotropins on ECFCs obtained from cord blood by assessing colony number, proliferation, migration, and sprouting ability. Moreover, we studied thrombin generation in ECFCs exposed to gonadotropins by performing a thrombin generation assay. Finally, we determined the levels of circulating gonadotropins in 30 men, to exclude the effect of estrogen, with lower extremity arterial disease (LEAD), in comparison with age- and sex-matched controls.
RESULTS
Exposure to FSH, LH, or PRL resulted in an increase in ECFC migration but showed no effect on proliferation or ECFC commitment from cord blood mononuclear cells. Using a three-dimensional fibrin gel assay, we showed that ECFC sprouting was significantly enhanced by gonadotropins. Exposure to FSH also increased the thrombin generation of ECFCs exposed to FSH. Finally, FSH and LH levels in men with LEAD were higher than those in controls.
CONCLUSION
Gonadotropins increase ECFC-related angiogenesis and may be involved in thrombin generation in cardiovascular disease. Gonadotropins may act as biomarkers; moreover, we hypothesize that gonadotropin-blocking strategies may be a novel interesting therapeutic approach in atherosclerotic cardiovascular disease.

Identifiants

pubmed: 34623025
doi: 10.1111/jth.15549
pii: S1538-7836(22)02732-5
doi:

Substances chimiques

Gonadotropins 0
Testosterone 3XMK78S47O

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

230-237

Informations de copyright

© 2021 International Society on Thrombosis and Haemostasis.

Références

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Auteurs

Grégoire Détriché (G)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.
Biosurgical Research Lab (Carpentier Foundation), Vascular Medicine Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France.

Nicolas Gendron (N)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.
Biosurgical Research Lab (Carpentier Foundation), Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France.

Aurélien Philippe (A)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.
Biosurgical Research Lab (Carpentier Foundation), Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France.

Maxime Gruest (M)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.
Biosurgical Research Lab (Carpentier Foundation), Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France.

Paul Billoir (P)

Vascular Hemostasis Unit, UNIROUEN, INSERM U1096, Rouen University Hospital, Normandie Univ, Rouen, France.

Elisa Rossi (E)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.

Coralie L Guerin (CL)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.
Cytometry Platform, Institut Curie, Paris, France.
Department of Infection and Immunity, Luxembourg Institute of Health, Strassen, Luxembourg.

Anna Lokajczyk (A)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.

Séverine Brabant (S)

AP-HP, Department of Functional Explorations, Necker Enfants Malades Hospital, Paris-Centre University, Paris Cedex, France.

Dominique Prié (D)

AP-HP, Department of Functional Explorations, Necker Enfants Malades Hospital, Paris-Centre University, Paris Cedex, France.

Tristan Mirault (T)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.
Biosurgical Research Lab (Carpentier Foundation), Vascular Medicine Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France.

David M Smadja (DM)

INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France.
Biosurgical Research Lab (Carpentier Foundation), Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France.

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