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
ABSTRACT 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.
SourceAvailable from: Andrea M Isidori[Show abstract] [Hide abstract]
ABSTRACT: The myocardial effects of phosphodiesterase type 5 inhibitors (PDE5i) have recently received consideration in several preclinical studies. The risk/benefit ratio in humans remains unclear.BMC Medicine 10/2014; 12(1):185. DOI:10.1186/s12916-014-0185-3 · 7.28 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Previous studies established the efficacy of once-daily tadalafil for men with erectile dysfunction. However, no trial has focused on the effects of such treatment on men without previous experience using oral phosphodiesterase type 5 (PDE5) inhibitors. Subjects were randomized (2:1) to once-daily tadalafil 5 mg (with possible down-titration to 2.5 mg; n = 146) or placebo (n = 69) for 12 weeks. Among 215 subjects (mean age = 52 years), once-daily tadalafil treatment resulted in 61.7% of study participants reporting their ability to achieve and maintain erections being much better or very much better (vs. 21.7% on placebo; P < .001). Tadalafil significantly improved treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS; P < .001 vs. placebo at endpoint) and psychosocial outcomes on the Self-Esteem and Relationship (SEAR) questionnaire (least-squares mean difference in SEAR total score change from baseline = 11.8 [95% CI = 5.4-18.2; P < .001 vs. placebo]). Subjects receiving once-daily tadalafil also experienced a higher proportion of daily self-reported spontaneous morning erections at endpoint (58.7%) compared to placebo (42.2%; P < .001 for the between-treatment difference in changes from baseline). However, no significant differences in parameters of endothelial dysfunction (including biomarkers and peripheral arterial tonometric measures) or nocturnal erections as recorded by the nocturnal electrobioimpedance volumetric assessment were observed between treatment groups. Tadalafil was well tolerated; adverse events included back pain, headache, and dyspepsia. These findings may contribute to a more comprehensive understanding of once-daily tadalafil's effects on PDE5-inhibitor-naive men.Journal of Andrology 07/2012; 33(6). DOI:10.2164/jandrol.111.015289 · 1.69 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The number of the circulating angiogenic cells (CACs) and colony forming units (CFUs) derived from cultured circulating mononuclear cells (MNCs) represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction (ED) and vascular risk factors (VRFs) showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4 weeks of treatment with tadalafil (20 mg every other day) or with a placebo. The tadalafil treatment improved erectile function (P = 0.0028), but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 (P = 0.011) and tissue type plasminogen activator (P = 0.005) were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.Asian Journal of Andrology 12/2013; 16(2). DOI:10.4103/1008-682X.122347 · 2.53 Impact Factor