Klotho protein and atherosclerotic cardiovascular diseases: prolonging the thread of life

Abstract

To date, the most widely used biomarkers are natriuretic peptides and cardiac troponins. Many other biomarkers have also been identified, but only a few of them have found application in actual clinical practice. This review focuses on the Klotho protein and its role in cardiovascular diseases. In 1997, a gene that slows down the aging process was identified. It was named Klotho (Greek, ώ, spinning; Latin, Clotho; English, Klotho) in honor of the goddess of ancient Greek mythology, spinning the thread of life and being the personification of the steady, calm course of fate. Mice with an insertional mutation in the region of the Klotho gene promoter were characterized by premature aging processes. Three families of Klotho are known: -Klotho, -Klotho, and -Klotho, and the most studied is -Klotho. The Klotho protein consists of a large extracellular domain and a short C-terminal intracellular region. The extracellular domain consists of two repeat sequences called KL1 and KL2. -Klotho and -Klotho contain the KL1 and KL2 domains, respectively, and -Klotho contains only the KL1 domain. The Klotho gene in humans is located on chromosome 13q12 and consists of five exons. The Klotho protein is mainly expressed in the distal convoluted tubules of the kidneys and the vascular epithelial plexus of the cerebral ventricles. At lower concentrations, the Klotho gene is also found in other organs and tissues, particularly in the heart. Many studies have demonstrated the protective role of the Klotho protein in cardiovascular pathology. The pleiotropic properties of this protein are reflected in the diversity and interaction of cardioprotective mechanisms. The regulation of the concentrations of the Klotho protein in the blood and its expression in heart cells with the help of drugs can play a significant role in cellular metabolism and represent a promising target for the treatment of heart and vascular pathologies.