Endothelial dysfunction occurs prior to clinical evidence of polycystic kidney disease.
Endothelial dysfunction occurs prior to clinical evidence of polycystic kidney disease.
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DOI：
10.1159/000354236
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发表时间：
2013
影响因子：
4.2
通讯作者：
Rodriguez-Porcel M
中科院分区：
文献类型：
--
作者：
Peterson KM;Franchi F;Loeffler DL;Psaltis PJ;Harris PC;Lerman LO;Lerman A;Rodriguez-Porcel M
多囊肾病（PKD）是一种常染色体显性遗传或常染色体隐性遗传的单基因疾病（ARPKD），是肾功能不全和终末期肾衰竭的最常见遗传原因。除了囊肿的发展，常染色体形式的PKD与血管内皮功能障碍有关，血管内皮功能障碍是血管疾病的标志。血管内皮功能障碍是否也存在于ARPKD中，以及与肾功能不全的关系仍有待确定。在6周龄和10周龄对ARPKD大鼠（PCK模型）和对照组进行研究，并测量平均动脉压（MAP）和肾功能。采用器官室技术评估主动脉内皮功能。主动脉内皮细胞（ECs）的分离，其特征和功能的研究。与对照组相比，ARPKD动物对内皮依赖性血管舒张剂的血管舒张作用降低，甚至在MAP或肾功能变化之前。异常的血管反应性被纠正与L-精氨酸（前体的一氧化氮），而内皮型一氧化氮合酶（eNOS）的表达是不变的。此外，从6周龄ARPKD动物分离的内皮细胞显示出增加的氧化应激，保留eNOS表达和异常的迁移模式和血管生成能力（分别通过划痕和管形成试验测量）。ARPKD在早期阶段导致主动脉血管功能和EC受损，这可能具有显著的功能后果，可能代表该疾病的新治疗靶点。
Polycystic kidney disease (PKD), a monogenic disease with an autosomal dominant or an autosomal recessive form of inheritance (ARPKD), is the most common genetic cause of renal dysfunction and end stage renal failure. In addition to the development of cysts, the autosomal form of PKD is associated with vascular endothelial dysfunction, a marker of vascular disease. Whether vascular endothelial dysfunction is also present in ARPKD, and the relationship with renal dysfunction remains to be determined. ARPKD rats (PCK model) and controls were studied at 6 and 10 weeks of age, and mean arterial pressure (MAP) and renal function were measured. Aortic endothelial function was assessed using organ chamber techniques. Aortic endothelial cells (ECs) were isolated, characterized and their function studied. Compared to controls, ARPKD animals had a decrease in the vasorelaxation to endothelium-dependent vasodilators, even prior to changes in MAP or renal function. The abnormal vasoreactivity was corrected with L-arginine (precursor to nitric oxide), while the expression of endothelial nitric oxide synthase (eNOS) was unchanged. Furthermore, isolated ECs from 6 week-old ARPKD animals showed increased oxidative stress, with preserved eNOS expression and abnormal patterns of migration and angiogenic capacity (measured by the scratch and tube formation assays, respectively). ARPKD leads to impaired aortic vascular function and ECs at an early stage, which can have significant functional consequences, potentially representing a novel therapeutic target in this disease.
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影响因子：
10.5
作者：
Harris PC;Torres VE
通讯作者：
Torres VE
影响因子：
10.8
作者：
Rodriguez-Porcel, M;Lerman, LO;Lerman, A
通讯作者：
Lerman, A
DOI：
10.1073/pnas.0408518102
发表时间：
2005-05-10
影响因子：
11.1
作者：
Tao, YX;Kim, J;Edelstein, CL
通讯作者：
Edelstein, CL
影响因子：
11.1
作者：
Torres, V. E.;Harris, P. C.
通讯作者：
Harris, P. C.
影响因子：
19.6
作者：
Wang, D;Iversen, J;Strandgaard, S
通讯作者：
Strandgaard, S