ABSTRACT
The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease (CVD). The inactivation of the klotho gene causes serious systemic disorders resembling human aging, such as atherosclerosis, diffuse vascular calcification and shortened life span. Klotho has been demonstrated to ameliorate vascular endothelial dysfunction and delay vascular calcification. Furthermore, klotho gene polymorphisms in the human are associated with various cardiovascular events. Recent experiments show that klotho may reduce transient receptor potential canonical6 (TRPC6) channels, resulting in protecting the heart from hypertrophy and systolic dysfunction. Fibroblast growth factor23 (FGF23) is a bone-derived hormone that plays an important role in the regulation of phosphate and vitamin D metabolism. FGF23 accelerates urinary phosphate excretion and suppresses 1,25-dihydroxy vitaminD3 (1,25(OH)2D3) synthesis in the presence of FGF receptor1 (FGFR1) and its co-receptor klotho, principally in the kidney. The hormonal affects of circulating klotho protein and FGF23 on vascular and heart have contributed to an understanding of their roles in the pathophysiology of arterial stiffness and left ventricular hypertrophy. Klotho and FGF23 appear to play a critical role in the pathogenesis of vascular disease, and may represent a novel potential therapeutic strategy for clinical intervention.
