Foresta Carlo, Di Mambro Antonella, Caretta Nicola, De Toni Luca, Zuccarello Daniela, Ferlin Alberto
Department of Histology, Microbiology and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, Padova, Italy.
Clin Endocrinol (Oxf). 2009 Sep;71(3):412-6. doi: 10.1111/j.1365-2265.2008.03507.x. Epub 2008 Dec 15.
Endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. Circulating EPC concentration is low in conditions characterized by endothelial dysfunction but their number can be increased by treatment with phosphodiesterase-5 (PDE5) inhibitors. EPCs are also reduced in hypogonadal men and testosterone (T) treatment restores their concentration.
To evaluate the relationship between the effect of PDE5 inhibitors and T on EPCs, we analysed the acute effect of vardenafil on the number of EPCs in hypogonadotrophic hypogonadal (HH) patients, before and after T treatment.
A case-control study at a university andrology centre.
Fifteen HH subjects and 25 aged-matched controls.
The number of circulating EPCs and progenitor cells (PCs) in HH patients was evaluated after acute vardenafil administration at baseline and after 6 months of T supplementation.
At baseline, HH men had significantly lower numbers of PCs and EPCs with respect to controls and vardenafil administration had no effect on the number of these cells. After 6 months of T treatment, all HH patients were eugonadal. With respect to baseline, PCs and EPCs were significantly higher and reached the levels observed in controls. Vardenafil administration in HH men at the end of T treatment induced a significant increase in PCs and EPCs in a manner similar to that in controls.
This study showed that normal T levels are necessary to restore the responsiveness of EPCs to PDE5 inhibitors, suggesting that T positively modulates PDE5 in bone marrow.
内皮祖细胞(EPCs)是内皮修复所需的骨髓来源细胞。在内皮功能障碍的情况下,循环EPC浓度较低,但通过磷酸二酯酶-5(PDE5)抑制剂治疗可增加其数量。性腺功能减退男性的EPCs数量也会减少,而睾酮(T)治疗可恢复其浓度。
为了评估PDE5抑制剂和T对EPCs的影响之间的关系,我们分析了伐地那非对性腺功能减退性性腺功能减退(HH)患者在T治疗前后EPCs数量的急性影响。
在一所大学男科中心进行的病例对照研究。
15名HH受试者和25名年龄匹配的对照者。
在基线时以及补充T 6个月后,对HH患者急性给予伐地那非后,评估循环EPCs和祖细胞(PCs)的数量。
在基线时,HH男性的PCs和EPCs数量相对于对照组显著更低,且伐地那非给药对这些细胞的数量没有影响。T治疗6个月后,所有HH患者性腺功能恢复正常。与基线相比,PCs和EPCs显著更高,并达到了对照组观察到的水平。在T治疗结束时,对HH男性给予伐地那非,可使PCs和EPCs显著增加,其方式与对照组相似。
本研究表明,正常的T水平对于恢复EPCs对PDE5抑制剂的反应性是必要的,提示T对骨髓中的PDE5具有正向调节作用。