Androgen stimulates endothelial cell proliferation via an androgen receptor/VEGF/cyclin A-mediated mechanism. Academic Article uri icon

Overview

abstract

  • Growing evidences support that androgen displays beneficial effects on cardiovascular functions although the mechanism of androgen actions remains to be elucidated. Modulation of endothelial cell growth and function is a potential mechanism of androgen actions. We demonstrated in the present study that androgens [dihydrotestosterone (DHT) and testosterone], but not 17β-estradiol, produced a time- and dose-dependent induction of cell proliferation in primary human aortic endothelial cells (HAECs) as evident by increases in viable cell number and DNA biosynthesis. Real-time qRT-PCR analysis showed that DHT induced androgen receptor (AR), cyclin A, cyclin D1, and vascular endothelial growth factor (VEGF) gene expression in a dose- and time-dependent manner. The addition of casodex, a specific AR antagonist, or transfection of a specific AR siRNA blocked DHT-induced cell proliferation and target gene expression, indicating that the DHT effects are mediated via AR. Moreover, coadministration of SU5416 to block VEGF receptors, or transfection of a specific VEGF-A siRNA to knockdown VEGF expression, produced a dose-dependent blockade of DHT induction of cell proliferation and cyclin A gene expression. Interestingly, roscovitine, a selective cyclin-dependent kinase inhibitor, also blocked the DHT stimulation of cell proliferation with a selective inhibition of DHT-induced VEGF-A expression. These results indicate that androgens acting on AR stimulate cell proliferation through upregulation of VEGF-A, cyclin A, and cyclin D1 in HAECs, which may be beneficial to cardiovascular functions since endothelial cell proliferation could assist the repair of endothelial injury/damage in cardiovascular system.

publication date

  • January 21, 2011

Research

keywords

  • Cyclin A
  • Dihydrotestosterone
  • Endothelium, Vascular
  • Receptors, Androgen
  • Testosterone
  • Vascular Endothelial Growth Factor A

Identity

PubMed Central ID

  • PMC3075033

Scopus Document Identifier

  • 79955066279

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.01210.2010

PubMed ID

  • 21257919

Additional Document Info

volume

  • 300

issue

  • 4