A sex-specific role for androgens in angiogenesis

Abstract

Mounting evidence suggests that in men, serum levels of testosterone are negatively correlated to cardiovascular and all-cause mortality. We studied the role of androgens in angiogenesis, a process critical in cardiovascular repair/regeneration, in males and females. Androgen exposure augmented key angiogenic events in vitro. Strikingly, this occurred in male but not female endothelial cells (ECs). Androgen receptor (AR) antagonism or gene knockdown abrogated these effects in male ECs. Overexpression of AR in female ECs conferred androgen sensitivity with respect to angiogenesis. In vivo, castration dramatically reduced neovascularization of Matrigel plugs. Androgen treatment fully reversed this effect in male mice but had no effect in female mice. Furthermore, orchidectomy impaired blood-flow recovery from hindlimb ischemia, a finding rescued by androgen treatment. Our findings suggest that endogenous androgens modulate angiogenesis in a sex-dependent manner, with implications for the role of androgen replacement in men.

Yaşlı Farelerin Beyninde Testosteron Takviyesinin Anjiyogenik Etkisi

“…It was determined that androgens stimulate erythropoietin production via VEGF in cell culture and endothelial stem cells are regulated hormonally. In the reduced level of these hormones due to castration angiogenesis is also downward as it was shown previously [7] . The changes due to castration includes the decrease in endothelial function of vessel (Arteria femoralis) and deterioration in calcium channel activity as a result of decrease in testosterone level and the absence of androgen receptor in testicular feminized mice [11] .…”

“…Few studies have been made regarding the effects of androgens on angiogenesis [6,7] . It was determined that androgens stimulate erythropoietin production via VEGF in cell culture and endothelial stem cells are regulated hormonally.…”

“…Castration in young male mice caused decrease in androgen receptors in the brain up to ten times [12] . Also using ischemic injury in male the effect of endogenous androgens in maintaining neovascularization was shown [7] . The results that castration decreased angiogenesis in male animals by lack of testosterone were led to investigations [13] , castration caused decreased vascular density in the normal tissue surrounding the tumor and consequently increased tumor hypoxia and apoptosis, and moderately decreased tumor growth in prostate.…”

“…In the absence of these hormones by means of castration, angiogenesis is downward [7] . According to Sordello and colleagues testosterone caused an increase in transcription and biological activity of VEGF in human prostate cell culture [15] .…”

“…by expression and releasing of angiogenic factors in female [3][4][5] . There are few and limited studies about the effect of testosterone on angiogenesis [6,7] . In addition to the factors mentioned above angiogenesis are also affected by the age.…”