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

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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, Κλωθώ, “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: α-Klotho, β-Klotho, and γ-Klotho, and the most studied is α-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. α-Klotho and β-Klotho contain the KL1 and KL2 domains, respectively, and γ-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.

About the authors

Amina M. Alieva

Pirogov Russian National Research Medical University (Pirogov Medical University)

Author for correspondence.
Email: amisha_alieva@mail.ru
ORCID iD: 0000-0001-5416-8579
SPIN-code: 2749-6427

MD, Cand. Sci. (Med.), associate professor;

Russian Federation, Moscow

Elena V. Reznik

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: elenaresnik@gmail.com
ORCID iD: 0000-0001-7479-418X
SPIN-code: 3494-9080

MD, Dr. Sci. (Med.), professor

Russian Federation, Moscow

Natalia V. Teplova

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: teplova.nv@yandex.ru
ORCID iD: 0000-0002-7181-4680
SPIN-code: 9056-1948

MD, Dr. Sci. (Med.), professor

Russian Federation, Moscow

Kira V. Voronkova

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: kiravoronkova@yandex.ru
ORCID iD: 0000-0003-1111-6378
SPIN-code: 1636-7627

MD, Dr. Sci. (Med.), professor

Russian Federation, Moscow

Elvira Azretalievna Khachirova

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: elchik09@mail.ru
ORCID iD: 0000-0003-2523-8907

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Leyla R. Sarakaeva

Almazov National Medical Research Center

Email: sarale723@gmail.com
ORCID iD: 0000-0002-2752-861X

PhD student

Russian Federation, Saint Petersburg

Ramiz K. Valiev

The Loginov Moscow Clinical Scientific Center

Email: radiosurgery@bk.ru
ORCID iD: 0000-0003-1613-3716
SPIN-code: 2855-2867

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Irina A. Kotikova

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: kotikova.ia@mail.ru
ORCID iD: 0000-0001-5352-8499
SPIN-code: 1423-7300

student

Russian Federation, Moscow

Igor G. Nikitin

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: igor.nikitin.64@mail.ru
ORCID iD: 0000-0003-1699-0881
SPIN-code: 3595-1990

MD, Dr. Sci. (Med.), professor

Russian Federation, Moscow

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Copyright (c) 2022 Alieva A.M., Reznik E.V., Teplova N.V., Voronkova K.V., Khachirova E.A., Sarakaeva L.R., Valiev R.K., Kotikova I.A., Nikitin I.G.

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