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

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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.