Faculty of Medicine of Universidade do Porto, Porto, Portugal.
J Sex Med. 2011 May;8(5):1341-51. doi: 10.1111/j.1743-6109.2010.02116.x. Epub 2010 Nov 22.
Aging is a recognized risk factor for erectile dysfunction (ED), contributing independently to vascular damage of penile tissue. Vascular maintenance depends on angiogenic balance in tissues. Vascular endothelial growth factor (VEGF) is a modulator of endothelial cells functions, after engagement to specific receptor kinase domain region (KDR). Other factors, such as angiopoietins, cross talk with VEGF, modulating its effects. Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) compete for binding to Tie-2 and, while Ang1 promotes vascular stabilization, Ang2 acts as a partial agonist or antagonist of Ang1 signaling, depending on VEGF bioavailability.
To quantify the expression of Ang1, Ang2, Tie-2, VEGF, and KDR by real-time polymerase chain reaction (PCR) in human corpus cavernosum (CC) from young and aged healthy individuals.
Human CC fragments were obtained from organ donors without known risk factors to ED and divided in two groups: young (16-35 years) and aged (59-74 years). RNA was extracted and converted to cDNA. Real-time PCR reactions employed appropriate primers. KDR, Tie-2, Akt, and phospho-Akt protein levels were also assessed by Western blotting (WB). Computer-assisted evaluation of vascular areas was performed.
Study of angiopoietins-Tie-2 and VEGF-KDR systems in human CC during aging by real-time PCR and WB. The ratios Ang1/Tie-2 and VEGF/KDR and Akt levels were also determined.
Real-time PCR results showed a sixfold significant reduction in the Ang1/Tie-2 ratio during aging. Ang2, VEGF, and KDR expression results were highly variable. Nevertheless, the ratio VEGF/KDR was significantly higher in the aged individuals. Akt and phospho-Akt levels were similar in both groups. Immunohistological evaluation revealed a significant decrease in vascular areas and endothelial surface in CC with aging, despite no differences found in vessel number.
The obtained results suggest an aging-associated downregulation of angiopoietins/Tie-2 system and an apparent compensatory upregulation of the VEGF/KDR system.
衰老被认为是勃起功能障碍（ED）的一个危险因素，它会导致阴茎组织的血管损伤。血管的维持依赖于组织中的血管生成平衡。血管内皮生长因子（VEGF）是一种调节内皮细胞功能的物质，与特定的受体激酶结构域（KDR）结合后发挥作用。其他因素，如血管生成素，与 VEGF 相互作用，调节其作用。血管生成素-1（Ang1）和血管生成素-2（Ang2）竞争与 Tie-2 结合，而 Ang1 促进血管稳定，Ang2 则作为 Ang1 信号的部分激动剂或拮抗剂，这取决于 VEGF 的生物利用度。
通过实时聚合酶链反应（PCR）定量检测年轻和老年健康个体阴茎海绵体（CC）中 Ang1、Ang2、Tie-2、VEGF 和 KDR 的表达。
从无 ED 已知危险因素的器官捐献者中获得 CC 组织片段，并将其分为两组：年轻组（16-35 岁）和老年组（59-74 岁）。提取 RNA 并转化为 cDNA。实时 PCR 反应采用适当的引物。还通过 Western 印迹（WB）评估 KDR、Tie-2、Akt 和磷酸化 Akt 蛋白水平。通过计算机辅助评估血管面积。
通过实时 PCR 和 WB 研究人类 CC 中血管生成素-Tie-2 和 VEGF-KDR 系统在衰老过程中的变化，并测定 Ang1/Tie-2 和 VEGF/KDR 比值以及 Akt 水平。
实时 PCR 结果显示，Ang1/Tie-2 比值在衰老过程中显著降低了 6 倍。Ang2、VEGF 和 KDR 的表达结果差异很大。然而，老年组的 VEGF/KDR 比值明显更高。两组的 Akt 和磷酸化 Akt 水平相似。免疫组织化学评估显示，随着年龄的增长，CC 中的血管面积和内皮表面显著减少，尽管血管数量没有差异。
研究结果表明，衰老与血管生成素/Tie-2 系统下调有关，而 VEGF/KDR 系统似乎代偿性上调。
