Gender dimorphisms in progenitor and stem cell function in cardiovascular disease

Abstract

Differences in cardiovascular disease outcomes between men and women have long been recognized and attributed, in part, to gender and sex steroids. Gender dimorphisms also exist with respect to the roles of progenitor and stem cells in post-ischemic myocardial and endothelial repair and regeneration. Understanding how these cells are influenced by donor gender and the recipient hormonal milieu may enable researchers to further account for the gender-related disparities in clinical outcomes as well as utilize the beneficial effects of these hormones to optimize transplanted cell function and survival. This review discusses (1) the cardiovascular effects of sex steroids (specifically estradiol and testosterone); (2) the therapeutic potentials of endothelial progenitor cells, mesenchymal stem cells, and embryonic stem cells; and (3) the direct effect of sex steroids on these cell types.

Keywords: Cardiovascular Disease; Gender Differences; Progenitor Cells; Sex Steroids; Stem Cell Therapy.

Fig. 1

After entering the cytoplasmic space, estrogen and androgen bind to and induce dimerization of their respective receptors. The dimers then translocate to the nucleus where they engage either estrogen response elements (ERE) or androgen response elements (ARE) to regulate gene transcription. ER estrogen receptor, AR androgen receptor

Fig. 2

Effects of estradiol on endothelial progenitor cell and mesenchymal stem cell function. EPC endothelial progenitor cell, MSC mesenchymal stem cell, VEGF vascular endothelial growth factor, HIF-1 hypoxia-inducible factor-1, BMP-2 bone morphogenetic protein-2