Estrogen induces endothelial progenitor cells proliferation and migration by estrogen receptors and PI3K-dependent pathways.
Estrogen induces endothelial progenitor cells (EPCs) migration and proliferation, which may serve as a potential target for coronary artery disease, but the mechanisms are unclear. We hypothesized that estrogen receptors (ERs) and phosphatidylinositol 3-kinase (PI3K) signaling pathway, which represent particularly important roles of action for estrogen, may contribute to estrogen-induced EPCs migration and proliferation. Bone marrow mononuclear cells (MNCs) were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with growth factors as previously described. A total of 87.32+/-5.13% of adherent cells showed uptake of acetylated low-density lipoprotein and lectin binding. Immunostaining and fluorescence activated cell sorting confirmed the endothelial progenitor phenotype. RT-PCR, immunocytochemistry staining and Western blot demonstrated expression of ERs. Exposure to 17beta-estradiol significantly improved EPCs migration and proliferation. Those effects were blocked by pretreatment with the pharmacological PI3K blockers LY294002 (1 h, 10 micromol/L) and ICI-182780 (1 h, 10 micromol/L), a specific estrogen receptor antagonist, which show involvement of estrogen receptors and PI3K pathway. These results suggest that estrogen induces EPCs migration and proliferation via ERs and PI3K pathway which provided a novel insight and treatment strategy of vascular biology.
Zhao
Xiaohui
X
Departments of Cardiovascular, XinQiao Hospital, University of Third Military Medical, ChongQing 400037, People's Republic of China.
Huang
Lan
L
Yin
Yangguang
Y
Fang
Yuqiang
Y
Zhao
Jinghong
J
Chen
Jianfei
J
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D002867:Chromones; D004958:Estradiol; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D000077267:Fulvestrant; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one