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Gender Dimorphisms in Progenitor and Stem Cell Function in Cardiovascular Disease

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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.

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Abbreviations

AR:

Androgen receptor

BMP-2:

Bone morphogenetic protein-2

CAD:

Coronary artery disease

E2:

17β-estradiol

eNOS:

Endothelial nitric oxide synthase

ER:

Estrogen receptor

EPC:

Endothelial progenitor cell

ESC:

Embryonic stem cell

FGF:

Fibroblast growth factor

HIF:

Hypoxia-inducible factor

IGF-1:

Insulin-like growth factor-1

IL:

Interleukin

I/R:

Ischemia/reperfusion

MI:

Myocardial infarction

MSC:

Mesenchymal stem cell

OVX:

Ovariectomized

SDF-1:

Stromal cell-derived factor-1

SOCS/3:

Suppressor of cytokine signaling

STAT3:

Signal transducer and activator of transcription

T:

Testosterone

TNF:

Tumor necrosis factor

TNFR:

Tumor necrosis factor receptor

VEGF:

Vascular endothelial growth factor

VEGR:

Vascular endothelial growth factor receptor

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Acknowledgments

This work was supported by the following NIH grants: R01 GM070628, R01 HL085595, F32 HL092718, F32 HL092719, and F32 HL093987.

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Authors and Affiliations

  1. Clarian Cardiovascular Surgery, Methodist Hospital, Indiana University School of Medicine, Indianapolis, IN, USA

    Arthur C. Coffey & Daniel R. Meldrum

  2. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    Jeremy L. Herrmann, Aaron M. Abarbanell, Brent R. Weil, Mariuxi C. Manukyan, Jeffrey A. Poynter, Yue Wang & Daniel R. Meldrum

  3. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA

    Daniel R. Meldrum

  4. Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN, USA

    Daniel R. Meldrum

  5. 635 Barnhill Drive, Van Nuys Medical Science Bldg Rm. #2017, Indianapolis, IN, 46202, USA

    Daniel R. Meldrum

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  1. Jeremy L. Herrmann
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Herrmann, J.L., Abarbanell, A.M., Weil, B.R. et al. Gender Dimorphisms in Progenitor and Stem Cell Function in Cardiovascular Disease. J. of Cardiovasc. Trans. Res. 3, 103–113 (2010). https://doi.org/10.1007/s12265-009-9149-y

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