| Budget Amount *help |
¥2,040,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
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
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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
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