Maeshima Yohei, Makino Hirofumi
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Fibrogenesis Tissue Repair. 2010 Aug 5;3:13. doi: 10.1186/1755-1536-3-13.
The number of patients requiring renal replacement therapy due to end-stage renal disease (ESRD) is increasing worldwide. The prevalence of chronic kidney disease (CKD), and the importance of CKD as a risk factor in development of ESRD and in complicating cardiovascular disease (CVD) have been confirmed. In recent years, the involvement of angiogenesis-related factors in the progression of CKD has been studied, and the potential therapeutic effects on CKD of modulating these factors have been identified. Vascular endothelial growth factor (VEGF)-A, a potent pro-angiogenic factor, is involved in the development of the kidney, in maintenance of the glomerular capillary structure and filtration barrier, and in the renal repair process after injury. VEGF-A is also involved in the development of early diabetic nephropathy, demonstrated by the therapeutic effects of anti-VEGF-A antibody. Angiopoietin (Ang)-1 induces the maturation of newly formed blood vessels, and the therapeutic effects of Ang-1 in diabetic nephropathy have been described. In experimental models of diabetic nephropathy, the therapeutic effects of angiogenesis inhibitors, including angiostatin, endostatin and tumstatin peptides, the isocoumarin NM-3, and vasohibin-1, have been reported.Further analysis of the involvement of angiogenesis-related factors in the development of CKD is required. Determining the disease stage at which therapy is most effective and developing an effective drug delivery system targeting the kidney will be essential for pro-or anti-angiogenic strategies for patients with CKD.
在全球范围内，因终末期肾病（ESRD）而需要肾脏替代治疗的患者数量正在增加。慢性肾脏病（CKD）的患病率以及CKD作为ESRD发展和心血管疾病（CVD）并发症危险因素的重要性已得到证实。近年来，已对血管生成相关因子在CKD进展中的作用进行了研究，并确定了调节这些因子对CKD的潜在治疗效果。血管内皮生长因子（VEGF）-A是一种强效促血管生成因子，参与肾脏发育、维持肾小球毛细血管结构和滤过屏障以及损伤后的肾脏修复过程。抗VEGF-A抗体的治疗效果表明，VEGF-A还参与早期糖尿病肾病的发展。血管生成素（Ang）-1诱导新形成血管的成熟，并且已经描述了Ang-1在糖尿病肾病中的治疗效果。在糖尿病肾病的实验模型中，已经报道了血管生成抑制剂的治疗效果，包括血管抑素、内皮抑素和tumstatin肽、异香豆素NM-3以及血管抑制素-1。需要进一步分析血管生成相关因子在CKD发展中的作用。确定治疗最有效的疾病阶段并开发针对肾脏的有效药物递送系统对于CKD患者的促血管生成或抗血管生成策略至关重要。
