Role of estrogen receptors in menstrual cycle–related neoangiogenesis and their influence on endothelial progenitor cell physiology

Objective

To study whether estrogen receptors (ERs) are expressed in vitro and in vivo by female circulating endothelial progenitor cells (EPCs); and the role of ERs in the periodic vascular damage and repair that occurs during the menstrual cycle.

Design

Quantification of circulating progenitor cells, EPCs, and relative CXCR4+ fraction by flow cytometry. Quantification of plasma 17β-E₂ by electrochemiluminescent immunoassay. Expression of ERs by immunofluorescence and immunohistochemistry. Estrogen receptor, CXCR4, and matrix metalloproteinase 9 gene expression by reverse transcriptase–polymerase chain reaction and real-time polymerase chain reaction.

Setting

University clinic and academic research laboratory.

Patient(s)

Twelve young fertile women (aged 22–27 years) observed for 6 months, 10 postmenopausal women (aged 52–63 years), and 50 male control subjects (aged 24–61 years).

Intervention(s)

Blood (35 mL) was collected at each observation point.

Main Outcome Measure(s)

Correlation between 17β-E₂ exposure and neoangiogenesis markers.

Result(s)

Estrogen receptors are expressed both in cultured EPCs after prolonged estrogen stimulation and in circulating EPCs, such as in CD34+ cells in bone marrow. The number of ER-β+ and CXCR4+ EPCs increased during the ovulatory phase, and this increase is probably mediated by ER-β and matrix metalloproteinase 9.

Conclusion(s)

Estrogens play a key role in neoangiogenesis processes, such as endometrium recovery, and this mechanism involves both a central action (on bone marrow) and a cytokine-mediated peripheral one (on endothelium).

Key Words: Endothelial progenitor cell, estrogen receptor, CXCR4, MMP9, menstrual cycle