[The protective role of Klotho gene on vascular endothelium].

Arteriosclerosis caused by aging is recognized to be a crucial risk factor of cardiovascular disease. We recently established Klotho mouse that causes age-related disorders including arteriosclerosis. The Klotho gene encodes a novel cell surface protein of 1014 amino acids. In humans, a secretory form of Klotho cDNA has been isolated, but the pathophysiological role of Klotho protein remains to be elucidated. We demonstrate that the vasodilator response of aorta to acetylcholine is significantly attenuated in and homozygous Klotho mice as compared with wild-type mice. Parabiosis between wild-type and heterozygous Klotho mice results in restoration of endothelial function in heterozygous Klotho mice. These results suggest that the Klotho protein protects the cardiovascular system through endothelium-derived NO production by humoral pathways.