title: Gender differences in endothelial progenitor cells and cardiovascular risk profile: the role of female estrogens.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPCs) participate in vascular homeostasis and angiogenesis. The aim of the present study was to explore EPC number and function in relation to cardiovascular risk, gender, and reproductive state.
  
  
  RESULTS
  As measured by flow-cytometry in 210 healthy subjects, CD34(+)KDR(+) EPCs were higher in fertile women than in men, but were not different between postmenopausal women and age-matched men. These gender gradients mirrored differences in cardiovascular profile, carotid intima-media thickness, and brachial artery flow-mediated dilation. Moreover, EPCs and soluble c-kit ligand varied in phase with menstrual cycle in ovulatory women, suggesting cyclic bone marrow mobilization. Experimentally, hysterectomy in rats was followed by an increase in circulating EPCs. EPCs cultured from female healthy donors were more clonogenic and adherent than male EPCs. Treatment with 17beta-estradiol stimulated EPC proliferation and adhesion, via estrogen receptors. Finally, we show that the proangiogenic potential of female EPCs was higher than that of male EPCs in vivo.
  
  
  CONCLUSIONS
  EPCs are mobilized cyclically in fertile women, likely to provide a pool of cells for endometrial homeostasis. The resulting higher EPC levels in women than in men reflect the cardiovascular profile and could represent one mechanism of protection in the fertile female population.
authors.affiliation: Clinical and Experimental Medicine, University of Padova Medical School, Italy. gianpaolofadini@hotmail.com
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.forename: Saula
authors.initials: S
authors.lastname: de Kreutzenberg
authors.forename: Mattia
authors.initials: M
authors.lastname: Albiero
authors.forename: Anna
authors.initials: A
authors.lastname: Coracina
authors.forename: Elisa
authors.initials: E
authors.lastname: Pagnin
authors.forename: Ilenia
authors.initials: I
authors.lastname: Baesso
authors.forename: Andrea
authors.initials: A
authors.lastname: Cignarella
authors.forename: Chiara
authors.initials: C
authors.lastname: Bolego
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Nardelli
authors.forename: Saverio
authors.initials: S
authors.lastname: Sartore
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008597:Menstrual Cycle / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593751:Atxn1 protein, rat; D004967:Estrogens; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011960:Receptors, Estrogen; D004958:Estradiol; D019009:Proto-Oncogene Proteins c-kit