Grégoire Détriché1,2, Nicolas Gendron1,3, Aurélien Philippe1,3, Maxime Gruest1,3, Paul Billoir4, Elisa Rossi1, Coralie L Guerin1,5,6, Anna Lokajczyk1, Séverine Brabant7, Dominique Prié7, Tristan Mirault1,2, David M Smadja1,3. 1. INSERM, Innovative Therapies in Haemostasis, Université de Paris, Paris, France. 2. Biosurgical Research Lab (Carpentier Foundation), Vascular Medicine Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France. 3. Biosurgical Research Lab (Carpentier Foundation), Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France. 4. Vascular Hemostasis Unit, UNIROUEN, INSERM U1096, Rouen University Hospital, Normandie Univ, Rouen, France. 5. Cytometry Platform, Institut Curie, Paris, France. 6. Department of Infection and Immunity, Luxembourg Institute of Health, Strassen, Luxembourg. 7. AP-HP, Department of Functional Explorations, Necker Enfants Malades Hospital, Paris-Centre University, Paris Cedex, France.
Abstract
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.
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.
Authors: Alexandros Rovas; Konrad Buscher; Irina Osiaevi; Carolin Christina Drost; Jan Sackarnd; Phil-Robin Tepasse; Manfred Fobker; Joachim Kühn; Stephan Braune; Ulrich Göbel; Gerold Thölking; Andreas Gröschel; Jan Rossaint; Hans Vink; Alexander Lukasz; Hermann Pavenstädt; Philipp Kümpers Journal: Angiogenesis Date: 2022-06-20 Impact factor: 10.658
Authors: Paul Philipp Heinisch; Corina Bello; Maximilian Y Emmert; Thierry Carrel; Martina Dreßen; Jürgen Hörer; Bernhard Winkler; Markus M Luedi Journal: Cells Date: 2022-05-18 Impact factor: 7.666
Authors: Grégoire Détriché; Alexis Guédon; Nassim Mohamedi; Olfa Sellami; Charles Cheng; Alexandre Galloula; Guillaume Goudot; Lina Khider; Hélène Mortelette; Jonas Sitruk; Nicolas Gendron; Marc Sapoval; Pierre Julia; David M Smadja; Tristan Mirault; Emmanuel Messas Journal: Front Cardiovasc Med Date: 2022-02-07