Therapeutic Approach for atherosclerosis with extensive calcification by replacement of Klotho protein

Klotho蛋白在肾脏中产生，并释放到循环中。肾损害患者血药浓度明显降低。Klotho缺陷小鼠表现出广泛的血管钙化，这与肾功能衰竭患者的情况相似。我们在这里研究了Klotho在维持血管内稳态中的作用，以及Klotho替代疗法预防血管钙化的可能性。5/6肾切除小鼠血清中Klotho水平降至对照水平的20%左右。向肾切除小鼠泵注血管紧张素II可诱导血管钙化。而应用Klotho-cDNA腺病毒或纯化的(His标记的)Klotho蛋白可显著减轻血管钙化。因此，我们的发现提示Klotho是在肾脏中产生的，以防止血管钙化，Klotho在肾功能衰竭患者中的替代可能是治疗血管钙化合并肾功能衰竭的有效方法。

Klotho protein is produced in the kidney and released into circulation. Its concentration in the patient with renal damage is markedly decreased. Klotho deficient mice show extensive vascular calcification which was similar to that of the patient with renal failure. We here studied the role of Klotho in the maintenance of vascular homeostasis and the possibility of Klotho replacement therapy to prevent vascular calcification. 5/6 nephrectomy in mice decreased Klotho level in the serum to ~20% of the control level. Pump infusion of Angiotensin II to the nephrectomized mice induce vascular calcification. Whereas, administration of Klotho-cDNA recombinant adenovirus or purified (His-tagged) Klotho protein markedly attenuated the vascular calcification. Thus, our finding suggested that Klotho is produced in the kidney to prevent vascular calcification and replacement of Klotho in the patient with renal failure may be effective therapy for vascular calcification with renal failure.