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

Department of Internal Medicine, University of L'Aquila, Italy.
Atherosclerosis (Impact Factor: 3.99). 01/2008; 196(1):313-9. DOI: 10.1016/j.atherosclerosis.2006.09.035
Source: PubMed


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.

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    • "A current hypothesis for the initial lesions of atherosclerosis as well as for the pathogenesis of erectile dysfunction (ED) involves endothelial cell damage/dysfunction.1 Elevated serum levels of cellular adhesion molecules (CAMs) released by a damaged endothelium are found under conditions associated with an increased risk of developing atherosclerosis and ED,23 with or without vascular diseases or vascular risk factors (VRFs).456 ED in men with VRFs or vascular diseases is associated with a dulled capacity for repairing endothelial damage, as suggested by a reduced number of bone marrow-derived circulating endothelial progenitor cells (PGCs) and by a reduced ability of ex vivo expanded blood mononuclear cells (MNCs) to form circulating angiogenic cells (CACs).7891011 Biochemical and functional surrogates of vascular damage and of a reduced endothelial cell repair ability, as well as epidemiologic studies,121314 suggest that ED is an early sign of a systemic vascular disease. "
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    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.
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    ABSTRACT: Descripción: El American College of Physicians desarrolló estas guías clínicas para presentar la evidencia disponible sobre la evaluación hormonal y el tratamiento farmacológico de la disfunción eréctil. Las terapéutica farmacológica actual incluye a los inhibidores de la 5-fosfodiesterasa (PDE-5) como el sildenafil, vardenafil, tadalafil, mirodenafil y udenafil, así como el tratamiento hormonal. Métodos: La literatura publicada sobre este tema fue identificada usando MEDLINE (1966 a mayo del 2007), EMBASE (1980 a la semana 22 del 2007), el Registro Central de Estudios Controlados Cochrane (segunda trimestre del 2007), PsycINFO (1985 a junio del 2007), AMED (1985 a junio del 2007), y SCOPUS (2006). La búsqueda bibligráfica fue actualizada buscando artículos en MEDLINE y EMBASE publicados entre mayo 2007 y abril 2009. Las búsquedas se limitaron a publicaciones en idioma inglés. Esta guía clínica establece el nivel de evidencia y el grado de recomendación utilizando el sistema de graduación de las guías clínicas del American College of Physicians.
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