The role of androgens in angiogenesis, endothelial progenitor cell mobilisation and endothelial cell function

Abstract

It is now recognised that cardiovascular repair mechanisms such as angiogenesis and endothelial progenitor cell (EPC)-mediated vasculogenesis are critical elements in the regenerative response to injury and ischaemia. Given the close relationship between EPCs, cardiovascular risk factors, CAD events, and angiogenesis, the studies in this thesis sought to investigate the effects of androgens on angiogenesis, EPC mobilisation, and endothelial function. The in vitro experiments of this thesis found that androgens stimulate the key angiogenic activities of two distinct EPC types - the early EPC and the late outgrowth endothelial cell (OEC). A randomised clinical trial was carried out to verify the above observations in a clinical trial setting. In this trial, young and old men were randomised to high dose testosterone therapy. Using flow cytometry analysis, androgen therapy did not appear to have any effect on circulating early EPCs numbers in either the ‘young’ or the ‘old’ group. However, testosterone therapy increased circulating OECs of men in the ‘old’ group but not in the ‘young’ group. The studies in this thesis provide a bench-to-bedside assessment on the effect of androgens on EPCs and angiogenesis via in vitro and in vivo pre-clinical experiments, and a randomised clinical trial.