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

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.

Women Specific Characteristics and 1-Year Outcome Among Patients Hospitalized for Peripheral Artery Disease: A Monocentric Cohort Analysis in a Tertiary Center

“…Women with a lower increase in FSH during their transition to menopause may be less at risk of atherosclerosis than those with a medium or high increase in FSH at the same period (37,38). Our team recently assessed the impact of gonadotropins in vitro on endothelial progenitor cells suggesting that gonadotropins blocking strategies could be a new interesting therapeutic approach in ASCVD (39).…”

Endothelial Progenitor Cells as Biomarkers of Cardiovascular Pathologies: A Narrative Review

“…In diabetic cardiomyopathy, treatment with BMP7, an anti-inflammatory protein, led to an increase in EPC markers and neovascularisation, ultimately improving cardiac remodelling [97]. Blocking hormonal pathways that are important in CVD development, such as gonadotropin, an enhancer of ECFC angiogenesis, and thrombin might also be beneficial [98]. Using EPCderived vesicles [99] or exosomes [100] further helps to mitigate the problematic isolation and culturing process of EPCs, thereby providing more efficient therapeutic options.…”

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study

“…In the literature, to our knowledge, no study had previously evaluated TG as a predictor of CVST evolution. TG assay is a global coagulation assay that may be altered in hypercoagulable states [ 12 , 33 ] or different types of endothelial injury [ [34] , [35] , [36] ]. In our study, lower ETP 5pM was associated only with hemorrhagic parenchymal lesion development.…”