Kang Duk-Hee, Kanellis John, Hugo Christian, Truong Luan, Anderson Sharon, Kerjaschki Dontscho, Schreiner George F, Johnson Richard J
*Baylor College of Medicine, Houston, Texas; University of Nurnberg, Nurnberg, Germany; Division of Nephrology, Oregon Health Sciences University and Portland Veterans Administration Medical Center, Portland, Oregon; Department of Clinical Pathology, University of Vienna, Vienna, Austria; Scios Inc, Sunnyvale, California; and Division of Nephrology, Ewha Women's University College of Medicine, Ewha Medical Research Center, Seoul, Korea.
J Am Soc Nephrol. 2002 Mar;13(3):806-816. doi: 10.1681/ASN.V133806.
The role of the vascular endothelium in progressive renal disease is not well understood. This review presents evidence that progressive renal disease is characterized by a progressive loss of the microvasculature. The loss of the microvasculature correlates directly with the development of glomerular and tubulointerstitial scarring. The mechanism is mediated in part by a reduction in the endothelial proliferative response, and this impairment in capillary repair is mediated by alteration in the local expression of both angiogenic (vascular endothelial growth factor) and antiangiogenic (thrombospondin 1) factors in the kidney. The alteration in balance of angiogenic growth factors is mediated by both macrophage-associated cytokines (interleukin-1beta) and vasoactive mediators. Finally, there is intriguing evidence that stimulation of angiogenesis and/or capillary repair may stabilize renal function and slow progression and that this benefit occurs independently of effects on BP or proteinuria. Therefore, angiogenic agents may represent a novel therapeutic approach for slowing the progression of renal disease.
血管内皮在进行性肾病中的作用尚未完全明确。本综述提供的证据表明，进行性肾病的特征是微血管逐渐丧失。微血管的丧失与肾小球和肾小管间质瘢痕形成直接相关。其机制部分是由内皮细胞增殖反应降低介导的，而这种毛细血管修复功能的损害是由肾脏中血管生成（血管内皮生长因子）和抗血管生成（血小板反应蛋白1）因子的局部表达改变介导的。血管生成生长因子平衡的改变是由巨噬细胞相关细胞因子（白细胞介素-1β）和血管活性介质共同介导的。最后，有引人关注的证据表明，刺激血管生成和/或毛细血管修复可能稳定肾功能并减缓疾病进展，且这种益处独立于对血压或蛋白尿的影响而产生。因此，血管生成剂可能代表一种减缓肾病进展的新型治疗方法。
