Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: A corrosion cast study

Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: A corrosion cast study
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DOI:
10.1038/sj.ki.5001725
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发表时间:
2006-10-01
影响因子:
19.6
通讯作者:
Bello-Reuss, E.
Bello-Reuss, E.
中科院分区:
医学1区
文献类型:
--
作者:
Wei, W.;Popov, V.;Bello-Reuss, E.

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常染色体显性多囊肾病(ADPKD)约占所有需要透析的慢性肾衰竭病例的10%。这种疾病的特征是肾上皮细胞的增殖和囊肿的形成,这些囊肿多年来扩大并取代正常的肾实质。随着囊肿的生长,肾脏的体积可以增加10倍以上,这意味着必须发生血管的重塑和扩张,为囊肿细胞提供氧合和营养。我们以前的研究支持ADPKD中存在血管生成的观点。我们在此报告ADPKD肾血管树脂铸型的结果。在这项研究中,腐蚀铸造法与扫描电子显微镜结合使用,以研究血管结构和血管生成的证据,在ADPKD肾脏。我们在囊肿周围发现了一个轮廓分明的血管网,形成一个类似于无血管平滑肌瘤的血管囊。我们还发现,正常的血管结构丢失,取而代之的是各种各样的毛细血管的大小比那些在正常的肾脏,混合扁平和螺旋形的小动脉,受损的肾小球,和闭锁的小静脉,表明微血管的退化。在相同的区域,有毛细血管发芽,被认为是血管生成的标志。本研究记录了血管系统的退行性变化,证实了ADPKD肾脏中存在血管生成,并建议使用血管生成抑制剂作为治疗该疾病的可能途径。
Autosomal-dominant polycystic kidney disease (ADPKD) accounts for about 10% of all cases of chronic renal failure requiring dialysis. The disease is characterized by proliferation of renal epithelial cells and formation of cysts that expand over years and replace the normal parenchyma of the kidney. As the cysts grow, the volume of the kidney can increase by more than 10-fold, implying that remodeling and expansion of the vasculature must occur to provide oxygenation and nutrition to the cyst cells. Our previous studies support the notion that there is angiogenesis in ADPKD. We report here results from resin casting of ADPKD kidneys vasculature. In this study, the corrosion-casting method was used in conjunction with scanning electron microscopy to study the vascular architecture and the evidence for angiogenesis in ADPKD kidneys. We found a well-defined vascular network around the cysts forming a 'vascular capsule' somewhat similar to that described in avascular leiomyomata. We also found that the normal vascular architecture is lost and replaced by an assortment of capillaries of larger size than those in the normal kidney, mixed with flattened and spiral arterioles, damaged glomeruli, and atresic venules, indicative of regression of the microvasculature. In the same areas, there was capillary sprouting, considered the hallmark of angiogenesis. The present study documents regression changes of the vasculature and confirms the existence of angiogenesis in ADPKD kidneys, and suggests the use of inhibitors of angiogenesis as a possible avenue for the treatment of the disease.