Sex Hormones Estradiol Stimulates Capillary Formation by Human Endothelial Progenitor Cells
نویسندگان
چکیده
Endothelial progenitor cells (EPCs) repair damaged endothelium and promote capillary formation, processes involving receptor tyrosine kinases (RTKs) and heme oxygenase 1 (HO-1). Because estradiol augments vascular repair, we hypothesize that estradiol increases EPC proliferation and capillary formation via RTK activation and induction of HO-1. Physiological concentrations of estradiol (10 nmol/L) increased EPC-induced capillary sprout and lumen formation in matrigel/fibrin/collagen systems. Propyl-pyrazole-triol (PPT; 100 nmol/L; estrogen receptor [ER]agonist), but not diarylpropionitrile (ERagonist), mimicked the stimulatory effects of estradiol on capillary formation, and methyl-piperidino-pyrazole (ERantagonist) abolished the effects of estradiol and PPT. Three different RTK activators (vascular endothelial growth factor, hepatocyte growth factor, and stromal derived growth factor 1) mimicked the capillary-stimulating effects of estradiol and PPT. SU5416 (RTK inhibitor) blocked the stimulatory effects of estradiol and PPT on capillary formation. Estradiol increased HO-1 expression by 2to 3-fold, an effect blocked by SU5416, and PPT mimicked the effects of estradiol on HO-1. The ability of estradiol to enhance capillary formation, increase expression of HO-1, and augment phosphorylation of extracellular signal–regulated kinase 1/2, Akt, and vascular endothelial growth factor receptor 2 was mimicked by its cell-impermeable analog BSA estradiol. Actinomycin (transcription inhibitor) did not alter the effects of estradiol on RTK activity or vascular endothelial growth factor secretion. We conclude that estradiol via ERpromotes EPC-mediated capillary formation by a mechanism that involves nongenomic activation of RTKs and HO-1 activation. Estradiol in particular and ERagonists in general may promote healing of injured vascular beds by promoting EPC activity leading to more rapid endothelial recovery and capillary formation after injury. (Hypertension. 2010;56:397-404.)
منابع مشابه
Estradiol stimulates capillary formation by human endothelial progenitor cells: role of estrogen receptor-{alpha}/{beta}, heme oxygenase 1, and tyrosine kinase.
Endothelial progenitor cells (EPCs) repair damaged endothelium and promote capillary formation, processes involving receptor tyrosine kinases (RTKs) and heme oxygenase 1 (HO-1). Because estradiol augments vascular repair, we hypothesize that estradiol increases EPC proliferation and capillary formation via RTK activation and induction of HO-1. Physiological concentrations of estradiol (10 nmol/...
متن کاملEstradiol Stimulates Capillary Formation by Human Endothelial Progenitor Cells Role of Estrogen Receptor- / , Heme Oxygenase 1, and Tyrosine Kinase
Endothelial progenitor cells (EPCs) repair damaged endothelium and promote capillary formation, processes involving receptor tyrosine kinases (RTKs) and heme oxygenase 1 (HO-1). Because estradiol augments vascular repair, we hypothesize that estradiol increases EPC proliferation and capillary formation via RTK activation and induction of HO-1. Physiological concentrations of estradiol (10 nmol/...
متن کامل3D study of capillary network derived from human cord blood mesenchymal stem cells and differentiated into endothelial cell with VEGFR2 protein expression
New blood forming vessels are produced by differentiation of mesodermal precursor cells to angioblasts that become endothelial cells (ECs) which in turn give rise to primitive capillary network. Human cord blood (HCB) contains large subsets of mononuclear cells (MNCs) that can be differentiated into endothelial-like cells in vitro. Human mononuclear progenitor cells were purified from fresh umb...
متن کاملCapillary Network Formation by Endothelial Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells
Human bone marrow derived mesenchymal stem cells (HBMSCs) have the potential to differentiate into cells such as adipocyte, osteocyte, hepatocyte and endothelial cells. In this study, the differentiation of hBMSCs into endothelial like-cells was induced in presence of vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF-1). The differentiated endothelial cells were exam...
متن کاملSpecification of Hemato-Endothelial-Like Structures and Generation of Hematopoietic Progenitor Cells from Human Pluripotent Stem Cells
Background and purpose: Human pluripotent stem cells (hPSCs) with the ability to differentiate into adult cells have provided a new perspective for treatment of some diseases. But, the efficiency of differentiation methods to generate hematopoietic progenitor cells (HPCs) is faced with multiple challenges. In the present study, we investigated the formation of hemato-endothelial-like structure...
متن کامل