Investigation into regenerative therapy by endothelial progenitor cells in chronic kidney injury

各种疾病是造成肾损害的原因。许多病理机制已被证明参与肾损伤的发展，最终导致尿毒症。在本研究中，我们着重探讨了血管生成障碍在肾损伤进展中的潜在作用，在肾大部切除大鼠中，肾单位和血管系统通过血压依赖性和非血压依赖性机制受到损伤。在血压非依赖性因素中，尿毒症环境在进行性肾损害中起重要作用。因此，贫血、高磷血症或继发性甲状旁腺功能亢进（过量的甲状旁腺激素（PTH））参与了肾和心脏血管系统的异常重塑。这些因素也是尿毒症大鼠心肌肥厚和纤维化的原因。此外，有研究表明，内皮祖细胞（EPCs）的异常可能与 关于我们 在尿毒症大鼠模型中，用促红细胞生成素刺激剂恢复贫血和用饮食限制、磷酸盐结合剂或甲状旁腺切除术治疗矿物质骨疾病不仅对肾损伤的进展，而且对心血管重塑具有有利的作用。与对照组相比，尿毒症大鼠或尿毒症患者循环EPCs的数量减少。此外，尿毒症环境中EPCs的功能也受损。在长期血液透析患者中，循环EPCs数量减少与合并症相关，包括卒中、心血管疾病和外周动脉疾病。这些结果提示，内皮祖细胞异常可能在尿毒症患者多种疾病的发病机制中起重要作用，内皮祖细胞异常与组织损伤中血管生成障碍有关。血管生成减少可能导致损伤组织长期缺氧状态，从而导致严重的缺血性损伤。少

Various disorders are responsible for renal impairment. Many pathomechanisms has been demonstrated to be involved in the development of kidney injury, which ultimately leads to uremia. In this study, we focused on the potential role of disturbed angiogenesis in the progression of renal damage.In subtotally nephrectomized rats, vascular system, as well as nephrons, was injured in remnant kidney through both blood-pressure-dependent and blood-pressure-independent mechanisms. It has been suggested that uremic milieu, among blood-pressure-independent factors, plays an important role in progressive renal damage. Thus, anemia, hyperphosphatemia, or secondary hyperparathyroidism (excessive parathyroid hormone(PTH)) were involved in abnormal remodeling of vascular system of kidney and heart. These factors were also responsible for cardiac hypertrophy and fibrosis in uremic rats. In addition, it was been suggested that abnormality in endothelial progenitor cells (EPCs) might be associated with … More disturbed angiogenesis, which is responsible for impaired tissue repair, in uremia.Restored anemia with erythropoietin-stimulating agent and treatment of mineral bone disorder with dietary restriction, phosphate binder, or parathyroidectomy have favorable effects not only on the progression of renal injury, but also on cardiovascular remodeling, in uremic rat model. The number of circulating EPCs was decreased in uremic rats or uremic patients as compared with control subjects. In addition, EPCs were also functionally impaired in uremic milieu. In long-term hemodialysis patients, decreased number of circulating EPCs was associated with comorbidities, including stroke, cardiovascular disease, and peripheral arterial disease. These results suggest abnormalities in EPCs might play a critical role in the pathogenesis of various disorders in uremic patients.Abnormalities in EPCs are associated impaired angiogenesis in tissue injury. Decreased angiogenesis might contribute to prolonged hypoxic state in injured tissue, which leads to profound ischemic damage. Less