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勃起功能障碍和代谢综合征患者循环内皮祖细胞和内皮微粒的新免疫表型:他达拉非给药的影响。

New immunophenotype of circulating endothelial progenitor cells and endothelial microparticles in patients with erectile dysfunction and metabolic syndrome: effects of tadalafil administration.

作者信息

La Vignera S

机构信息

Section of Endocrinology, Andrology and Internal Medicine, Human Reproduction and Biotechnology Sciences, Department of Internal Medicine and Systemic Diseases, University of Catania, Catania, Italy.

出版信息

Int Angiol. 2011 Oct;30(5):415-23.

Abstract

AIM

Circulating endothelial progenitor cells (EPCs) and endothelial microparticles (EMPs) increase, respectively, in the attempt to repair the damaged endothelium and in response to endothelial dysfunction. Erectile dysfunction (ED) of arterial origin recognizes endothelial dysfunction as one of its main determinants and shares risk factors and physiopathological evolution with the metabolic syndrome (MetS). Tadalafil, selective inhibitor of phosphodiesterase V, long half-life, is used to treat erectile dysfunction, and several studies have already documented the beneficial effects on endothelial dysfunction. The aim of this paper was to evaluate the concentrations of EPCs and EMPs in patients with arterial ED and MetS, before and after tadalafil administration, and in healthy men.

METHODS

Thirty patients (47-54 years) with ED and MetS (ATP III 1999 criteria) and 17 healthy men (44-57 years) were selected. EPCs (CD45neg/CD34pos/CD144pos) and EMPs (CD45neg/CD34neg/CD144pos) blood concentrations were evaluated by flow cytometry before and after administration of tadalafil (20 mg) on demand for 3 months. After treatment, the patients were divided into responders and poor responders, according to their IIEF-5 score.

MAIN OUTCOME MEASURES

Blood EPCs and EMPs.

RESULTS

Before treatment, the percentage of EPCs and EMPs was significantly higher in patients with ED and MetS compared to healthy men. Treatment with tadalafil increased significantly EPCs in both responders and poor responders. The latter had significantly higher EPCs compared to responders, both before and after tadalafil. Before tadalafil, EMPs were higher, but not significantly, in poor responders vs. responders. No significant change occurred after tadalafil administration in both responders and poor responders. A significant positive correlation was found between EPCs and age, Body Mass Index (BMI), acceleration time, IMT and EDV; whereas a negative correlation was found with IIEF-5 score, PSV and resistance index. EMPs correlated positively with BMI, acceleration time and IMT and negatively with the IIEF-5 score.

CONCLUSION

Tadalafil increased the percentage of EPCs in both responders and poor responders, suggesting the persistence of an adequate bone marrow response. The unchanged EMP concentrations after tadalafil suggest a reduction of the dysfunctional mechanism.

摘要

目的

循环内皮祖细胞(EPCs)和内皮微粒(EMPs)分别在试图修复受损内皮和对内皮功能障碍作出反应时增加。动脉源性勃起功能障碍(ED)将内皮功能障碍视为其主要决定因素之一,并与代谢综合征(MetS)共享风险因素和生理病理演变过程。他达拉非是一种磷酸二酯酶V的选择性抑制剂,半衰期长,用于治疗勃起功能障碍,多项研究已证明其对内皮功能障碍具有有益作用。本文旨在评估动脉性ED和MetS患者在服用他达拉非前后以及健康男性中EPCs和EMPs的浓度。

方法

选取30例年龄在47 - 54岁之间患有ED和MetS(符合1999年ATP III标准)的患者以及17名年龄在44 - 57岁之间的健康男性。通过流式细胞术评估按需服用他达拉非(20mg)3个月前后血液中EPCs(CD45阴性/CD34阳性/CD144阳性)和EMPs(CD45阴性/CD34阴性/CD144阳性)的浓度。治疗后,根据国际勃起功能指数-5(IIEF-5)评分将患者分为反应者和低反应者。

主要观察指标

血液中的EPCs和EMPs。

结果

治疗前,与健康男性相比,患有ED和MetS的患者中EPCs和EMPs的百分比显著更高。他达拉非治疗使反应者和低反应者的EPCs均显著增加。低反应者在服用他达拉非前后的EPCs均显著高于反应者。在服用他达拉非之前,低反应者的EMPs略高于反应者,但无显著差异。服用他达拉非后,反应者和低反应者的EMPs均无显著变化。EPCs与年龄、体重指数(BMI)、加速时间、内膜中层厚度(IMT)和舒张末期血流速度(EDV)呈显著正相关;而与IIEF-5评分、峰值收缩期血流速度(PSV)和阻力指数呈负相关。EMPs与BMI、加速时间和IMT呈正相关,与IIEF-5评分呈负相关。

结论

他达拉非使反应者和低反应者的EPCs百分比均增加,表明骨髓反应持续充足。他达拉非治疗后EMPs浓度未变,提示功能障碍机制有所减轻。

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