Implications of Klotho in vascular health and disease

Abstract

Cardiovascular disease (CVD) is a prevalent condition in general population and the first cause of death overall. Klotho, a pleiotropic protein related to longevity that acts as a co-receptor of the fibroblast growth factor 23, has been proposed as a key regulator of the development of CVD. In the few clinical studies made, it has been observed a relationship between low levels of soluble Klotho and the occurrence and severity of CVD, as well as a reduction of cardiovascular risk when they are high. Also, different polymorphisms of human Klotho gene have been related to the incidence of cardiovascular events. Moreover, several experimental studies indicate that this protein acts in the maintenance of vascular homeostasis. Klotho improves endothelial dysfunction through promotion of NO production and mediates anti-inflammatory and anti-aging effects such as suppression of adhesion molecules expression, attenuation of nuclear factor-kappa B or inhibition of Wnt signaling. Furthermore, this protein is related to the attenuation of vascular calcification as well as prevention of cardiac hypertrophy. The expression of this protein in the vascular wall implies a new scenario for the treatment of vascular disorders. The purpose of this review is to provide an overview of the relationship between the Klotho protein and CVD, in addition to its role in the maintenance of functional vascular integrity.

Keywords: Klotho, Cardiovascular disease, Vascular health, Aging, Endothelial dysfunction, Vascular calcification

Core tip: Cardiovascular disease (CVD) is the first cause of death worldwide. The anti-aging factor Klotho has been linked to the development of CVD since clinical studies relate circulating levels of Klotho with the appearance of vascular disease and different Klotho gene variants are associated with increased cardiovascular risk. Furthermore, Klotho is involved in promotion of vascular health through different mechanisms. The recent description of its expression in vascular tissue opens up new options for the treatment of cardiovascular diseases.