Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina
Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina
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DOI：
10.1159/000113755
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Hammes, Hans-Peter
中科院分区：
文献类型：
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作者：
Feng, Yuxi;Pfister, Frederick;Hammes, Hans-Peter
老年人的视网膜显示出血管退化的迹象。血管退化涉及血管生成素-2 (Ang-2) 和血管内皮生长因子 (VEGF) 表达之间的不匹配。我们使用杂合 Ang-2 缺陷 (Ang2LacZ) 小鼠来评估小鼠视网膜血管变化和生长因子的基因表达。通过定量视网膜形态测定法评估血管变化，并通过定量PCR测量生长因子的基因表达水平。 Ang2LacZ 视网膜中的内皮细胞和周细胞的数量并没有随着年龄的增长而变化，而在野生型视网膜中研究的整个年龄范围内，它们的数量都在减少。此外，杂合Ang2LacZ视网膜中的血管退化显着减慢（200%至1个月），而野生型视网膜中无细胞毛细血管的形成在13个月时显着增加（340%至1个月）。基因表达分析显示，野生型视网膜中 9 月龄时 VEGF、Ang-1、PDGF-B 和 Ang2 mRNA 水平下降。然而，与其他基因相比，Ang-2的下降幅度较小。与 1 个月相比，野生型小鼠的 VEGF 水平下降了 60%，而杂合 Ang-2 缺陷型视网膜的 VEGF 在 9 个月时增加了（1 个月时增加了 141%）。同样，野生型小鼠中的 Ang-1 水平下降（1 个月时下降 45%），但 Ang2LacZ 小鼠中的水平保持稳定。这些数据表明，随着年龄的增长，Ang-2 基因剂量的减少可以减缓视网膜的血管衰退。这种效应与较高水平的存活因子（例如 VEGF 和 Ang-1）有关，表明这些因子的比例对于毛细血管细胞的存活至关重要。版权所有 (c) 2008 S. Karger AG，巴塞尔。
Retinae of aged humans show signs of vascular regression. Vascular regression involves a mismatch between Angiopoietin-2 (Ang-2) and vascular endothelial growth factor ( VEGF) expression. We used heterozygous Ang-2 deficient (Ang2LacZ) mice to evaluate murine retinal vascular changes and gene expression of growth factors. Vascular changes were assessed by quantitative retinal morphometry and gene expression levels of growth factors were measured by quantitative PCR. The numbers of endothelial cells and pericytes did not change in the Ang2LacZ retinae with age, whereas they decreased throughout the age spectrum studied in the wild type retinae. Moreover, vascular regression significantly decelerated in the heterozygous Ang2LacZ retinae (200% to 1 month), while the formation of acellular capillaries was significantly increased at 13 months in the wild type retinae (340% to 1 month). Gene expression analysis revealed that VEGF, Ang-1, PDGF-B and Ang2 mRNA levels were decreased in the wild type retinae at 9 month of age. However, the decrease of Ang-2 was smaller compared with other genes. While VEGF levels dropped in wild type mice up to 60% compared to 1 month, VEGF increased in heterozygous Ang-2 deficient retinae at an age of 9 months (141% to 1 month). Similarly, Ang-1 levels decreased in wild type mice (45% to 1 month), but remained stable in Ang2LacZ mice. These data suggest that Ang-2 gene dose reduction decelerates vasoregression in the retina with age. This effect links to higher levels of survival factors such as VEGF and Ang-1, suggesting that the ratio of these factors is critical for capillary cell survival. Copyright (c) 2008 S. Karger AG, Basel.