Angiogenesis in autosomal-dominant polycystic kidney disease
Angiogenesis in autosomal-dominant polycystic kidney disease
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DOI：
10.1046/j.1523-1755.2001.00768.x
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发表时间：
2001-07-01
影响因子：
19.6
通讯作者：
Rajarman, S
中科院分区：
文献类型：
--
作者：
Bello-Reuss, E;Holubec, K;Rajarman, S
背景常染色体显性多囊肾病（ADPKD）是一种遗传性疾病，约占所有终末期肾病（ESRD）病例的10%。其特征在于上皮细胞囊肿的形成，细胞外基质的增加。以及被认为是囊肿压迫的结果的血管改变。我们最近的观察表明，丰富的血管网络上的囊肿的表面上，因此，我们推测，血管生成可能是ADPKD的进展的一个因素。采用（1）血管造影，（2）免疫染色[因子VIII相关抗原、血管内皮生长因子（VEGF）、VEGF受体1和2（VEGFR-1和VEGFR-2）、金属蛋白酶-2（MMP-2）和整合素α（v）β（3）和（3）蛋白质印迹分析和酶联免疫吸附试验]对从ADPKD患者中取出的肾脏进行研究。检测ADPKD细胞中VEGF（165）的表达。囊壁毛细血管网广泛; (2)血管畸形的形态学证据，（3）VEGF（165）在内皮细胞中VEGFR-2的囊肿细胞中的表达和内皮细胞中VEGFR-1的缺失，（4）培养的ADPKD囊肿细胞分泌VEGF（165），和（5）ADPKD血管中基质MMP-2和整合素α（v）β（3）的共表达。ADPKD中存在血管生成。这个过程可能是必要的囊肿细胞生长，并可能是负责增加血管通透性，促进液体分泌到囊肿。新生血管可能导致动脉瘤的形成，导致这种疾病的肾出血。
Background. Autosomal-dominant polycystic kidney disease (ADPKD) is a genetic disorder that is responsible for approximately 10% of all cases of end-stage renal disease (ESRD). It is characterized by the formation of epithelial cell cysts, an increase in the extracellullar matrix. and vascular alterations believed to be the result of compression by the cysts. Our recent observations demonstrated a rich vascular network on the surface of the cysts, and thus, we postulated that angiogenesis could be a factor in the progression of ADPKD.Methods. Kidneys removed from patients with ADPKD were studied using (1) angiographs, (2) immunostaining [factor VIII-related antigen, vascular endothelial growth factor (VEGF), VEGF receptors 1 and 2 (VEGFR-1 and VEGFR-2), metallo-proteinase-2 (MMP-2), and integrin alpha (v)beta (3) and (3) Western blot analysis and enzyme-linked immunosorbent assay. The expression of VEGF(165) in ADPKD cells in culture was determined.Results. There was (1) an extensive capillary network in the cyst wall of ADPKD kidneys. (2) morphological evidence of vascular malformations, (3) expression of VEGF(165) in cyst cells of VEGFR-2 in endothelial cells and an absence of VEGFR-1 in endothelial cells, (4) secretion of VEGF(165) by ADPKD cyst cells in culture, and (5) coexpression of matrix MMP-2 and integrin alpha (v)beta (3) in vessels from ADPKD.Conclusions. There is angiogenesis in ADPKD. This process may be necessary for cyst cells to grow and may be responsible for increased vascular permeability facilitating fluid secretion into the cysts. Neovascularization may result in the formation of aneurysms responsible for the renal bleeding in this disease.