Gender differences in endothelial progenitor cells and cardiovascular risk profile: the role of female estrogens.
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.
Fadini
Gian Paolo
GP
Clinical and Experimental Medicine, University of Padova Medical School, Italy. gianpaolofadini@hotmail.com
de Kreutzenberg
Saula
S
Albiero
Mattia
M
Coracina
Anna
A
Pagnin
Elisa
E
Baesso
Ilenia
I
Cignarella
Andrea
A
Bolego
Chiara
C
Plebani
Mario
M
Nardelli
Giovanni B
GB
Sartore
Saverio
S
Agostini
Carlo
C
Avogaro
Angelo
A
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
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