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 (20mg/other day) or placebo treatment. The number of ex vivo expanded functional CAC's, 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.
Bocchio
Massimo
M
Department of Internal Medicine, University of L'Aquila, Italy.
Pelliccione
Fiore
F
Department of Internal Medicine, University of L'Aquila, Italy.
Passaquale
Gabriella
G
Department of Internal Medicine, University of L'Aquila, Italy.
Mihalca
Radu
R
Department of Internal Medicine, University of L'Aquila, Italy.
Necozione
Stefano
S
Department of Internal Medicine, University of L'Aquila, Italy.
Desideri
Giovambattista
G
Department of Internal Medicine, University of L'Aquila, Italy.
Francavilla
Felice
F
Department of Internal Medicine, University of L'Aquila, Italy.
Ferri
Claudio
C
Department of Internal Medicine, University of L'Aquila, Italy.
Francavilla
Sandro
S
Department of Internal Medicine, University of L'Aquila, Italy. Electronic address: sandrof@univaq.it.
D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012307:Risk Factors; D000068581:Tadalafil; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5