Inhibition of phosphodiesterase type 5 with tadalafil is associated to an improved activity of circulating angiogenic cells in men with cardiovascular risk factors and erectile dysfunction

Circulating angiogenic cells (CACs) contribute to repair of the vessel wall and dysfunctional CACs are associated to endothelial dysfunction in men with vascular risk factors (VRFs). We investigated whether inhibition of phosphodiesterase type 5 (PDE5) in men with erectile dysfunction (ED) and VRFs is accompanied to changes of CACs and to changes of endothelial function. Thirty-six men with ED and VRFs were randomised to 4 weeks of tadalafil (20 mg/other day) or placebo treatment. The number of ex vivo expanded functional CACʹs, identified by uptake of 1,1′-dioctadecyl-3, 3,3′, 3′-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (DiLDL) and concomitant Ulex europaeus agglutinin I (UEA-1) binding, was determined at baseline and after treatment. The number of cells double positive for DiLDL and for UEA-1, per high-power field fluorescence microscopy was significantly reduced in patients compared to 10 controls (26.88 ± 6.3 and 74.41 ± 17.1, respectively; P < 0.0001) and was markedly increased after tadalafil treatment (40.69 ± 13.07 versus 25.82 ± 6.49; P < 0.0001). The percentage variation of CACs number and of flow-mediated dilation in the brachial artery by ultrasound after treatment was significantly associated to the presence of endothelial dysfunction at baseline. In conclusion, the increased number of functional CACs after tadalafil treatment suggests a beneficial effect of prolonged PDE5 inhibition on vascular homeostasis.