Department of Urology, Hospital de S. João, and Faculty of Medicine of Universidade do Porto, Portugal.
J Sex Med. 2010 Apr;7(4 Pt 1):1410-8. doi: 10.1111/j.1743-6109.2009.01648.x. Epub 2010 Jan 6.
Erectile dysfunction (ED) is a highly prevalent and age-related disease, caused by endothelial dysfunction and impaired cavernous angiogenesis. However, cellular and molecular changes involved in erectile pathophysiology in aging male remain to be elucidated.
To characterize the vascular organization, concomitantly with analysis of the expression of vascular endothelial growth factor (VEGF), Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2) in young and aged human corpus cavernosum.
Human penile fragments were removed from patients submitted to penile deviation surgery (11 cases; 58-70 years) and from potential organ donors (four cases; 18-28 years) without ED or risk factors for ED. Smooth muscle and connective tissue were assessed by Masson's trichrome staining and computer-assisted histomorphometry. Dual immunostaining for specific markers of endothelium (von Willebrand factor) and smooth muscle cell (alpha-actin), VEGF, Ang1 and Ang2 was assayed by fluorescence microscopy. Semi-quantification of expression of angiogenic factors was performed by Western blotting.
Expression of VEGF and Angiopoietins in human corpus cavernosum, using a combination of histologic stainings, and molecular biology tools in order to achieve a better understanding of cavernosal tissue remodeling with aging.
Aged human corpus cavernosum presented wider sinusoidal spaces, loss of muscle cell bundles, and increased connective tissue content. Ang1 was scarcely expressed in small clusters in smooth muscle cell cytoplasm with identical localization in both studied groups. VEGF expression was abundant in smooth muscle cell and its expression markedly decreased in aged tissue, contrasting with the expression of angiopoietins that increased in the aged corpus cavernosum.
Immunoflourescent studies of cellular markers and growth factors help clarifying vascular organization and angiogenesis mechanisms in erectile tissue. Our findings demonstrate that the organization pattern of vascular endothelium and smooth muscle components of cavernosal tissue modifies during aging. Ang1 and Ang2 upregulation in human-aged penile tissue suggest a VEGF-independent vascular remodeling mechanism.
勃起功能障碍（ED）是一种高度普遍且与年龄相关的疾病，由内皮功能障碍和海绵体血管生成受损引起。然而，与衰老男性勃起生理相关的细胞和分子变化仍有待阐明。
描述年轻和老年男性人体海绵体的血管组织，并分析血管内皮生长因子（VEGF）、血管生成素 1（Ang1）和血管生成素 2（Ang2）的表达。
从接受阴茎偏斜手术的患者（11 例；58-70 岁）和无勃起功能障碍或勃起功能障碍风险因素的潜在器官供体（4 例；18-28 岁）中取出阴茎片段。通过 Masson 三色染色和计算机辅助组织形态计量学评估平滑肌和结缔组织。通过荧光显微镜检测特定内皮标志物（血管性血友病因子）和平滑肌细胞（α-肌动蛋白）、VEGF、Ang1 和 Ang2 的双重免疫染色。通过 Western 印迹法对半定量分析血管生成因子的表达。
使用组织染色和分子生物学工具组合，评估人类海绵体中 VEGF 和血管生成素的表达，以更好地了解海绵体组织随年龄的重塑。
老年人体海绵体呈现更宽的窦状空间、肌束丢失和结缔组织含量增加。Ang1 在两组研究中均以相似的定位在平滑肌细胞细胞质中呈小簇状表达。VEGF 在平滑肌细胞中表达丰富，在老年组织中表达明显减少，而血管生成素的表达则在老年海绵体中增加。
细胞标志物和生长因子的免疫荧光研究有助于阐明勃起组织的血管组织和血管生成机制。我们的研究结果表明，在衰老过程中，海绵体组织的血管内皮和平滑肌成分的组织模式发生改变。在人类老年阴茎组织中，Ang1 和 Ang2 的上调表明存在一种 VEGF 独立的血管重塑机制。
