Russian MedicineRussian MedicineРоссийский медицинский журнал0869-21062412-9100Eco-Vector11082310.17816/medjrf110823ReviewsНаучные обзорыReview ArticleKlotho protein and atherosclerotic cardiovascular diseases: prolonging the thread of lifeБелок Klotho и атеросклеротические сердечно-сосудистые заболевания: продлевая нить жизниhttps://orcid.org/0000-0001-5416-85792749-6427AlievaAmina M.АлиеваАмина Магомедовна
Russian Federation

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

к.м.н., доцент

amisha_alieva@mail.ruhttps://orcid.org/0000-0001-7479-418X3494-9080ReznikElena V.РезникЕлена Владимировна
Russian Federation

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

д.м.н., профессор

elenaresnik@gmail.comhttps://orcid.org/0000-0002-7181-46809056-1948TeplovaNatalia V.ТепловаНаталья Вадимовна
Russian Federation

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

д.м.н., профессор

teplova.nv@yandex.ruhttps://orcid.org/0000-0003-1111-63781636-7627VoronkovaKira V.ВоронковаКира Владимировна
Russian Federation

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

д.м.н., профессор

kiravoronkova@yandex.ruhttps://orcid.org/0000-0003-2523-8907KhachirovaElvira AzretalievnaХачироваЭльвира Азреталиевна
Russian Federation

MD, Cand. Sci. (Med.)

к.м.н

elchik09@mail.ruhttps://orcid.org/0000-0002-2752-861XSarakaevaLeyla R.СаракаеваЛейла Рамазановна
Russian Federation

PhD student

аспирант

sarale723@gmail.comhttps://orcid.org/0000-0003-1613-37162855-2867ValievRamiz K.ВалиевРамиз Камраддинович
Russian Federation

MD, Cand. Sci. (Med.)

к.м.н

radiosurgery@bk.ruhttps://orcid.org/0000-0001-5352-84991423-7300KotikovaIrina A.КотиковаИрина Александровна
Russian Federation

student

студент

kotikova.ia@mail.ruhttps://orcid.org/0000-0003-1699-08813595-1990NikitinIgor G.НикитинИгорь Геннадиевич
Russian Federation

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

д.м.н., профессор

igor.nikitin.64@mail.ruPirogov Russian National Research Medical University (Pirogov Medical University)Российский национальный исследовательский медицинский университет имени Н.И. ПироговаAlmazov National Medical Research CenterНациональный медицинский исследовательский центр имени В.А. АлмазоваThe Loginov Moscow Clinical Scientific CenterМосковский клинический научно-практический центр им. А.С. Логинова04102022231120222853653800709202226092022Copyright ©; 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.Copyright ©; 2022, Алиева А.М., Резник Е.В., Теплова Н.В., Воронкова К.В., Хачирова Э.А., Саракаева Л.Р., Валиев Р.К., Котикова И.А., Никитин И.Г.2022Alieva 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.Алиева А.М., Резник Е.В., Теплова Н.В., Воронкова К.В., Хачирова Э.А., Саракаева Л.Р., Валиев Р.К., Котикова И.А., Никитин И.Г.https://creativecommons.org/licenses/by-nc-nd/4.0/https://medjrf.com/0869-2106/article/view/110823

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.

На сегодняшний день наиболее широко используемыми биомаркёрами являются натрийуретические пептиды и сердечные тропонины. Выявлено и множество других биомаркёров, но лишь немногие из них нашли применение в реальной клинической практике. Представленный обзор посвящён белку Klotho и его роли при сердечно-сосудистых заболеваниях.

В 1997 году был идентифицирован ген, замедляющий процессы старения. Его назвали Клото (греч. Κλωθώ — «прядущая»; лат. Clotho; англ. Klotho) в честь богини древнегреческой мифологии, прядущей нить жизни и являющейся олицетворением неуклонного, спокойного течения судьбы. Для мышей с инсерционной мутацией в области промотора гена Klotho были характерны процессы преждевременного старения. Известны три семейства Klotho: α-Klotho, β-Klotho и γ-Klotho; наиболее изученным являются α-Klotho. Белок Klotho состоит из большого внеклеточного домена и короткого С-концевого внутриклеточного участка. Внеклеточный домен состоит из 2 повторяющихся последовательностей, называемых KL1 и KL2; α-Klotho, β-Klotho содержат домены KL1 и KL2; γ-Klotho содержит только домен KL1. Ген Klotho у человека расположен на хромосоме 13q12 и состоит из 5 экзонов. Белок Klotho в основном экспрессируется в дистальных извитых канальцах почек и сосудисто-эпителиальном сплетении желудочков головного мозга. В более низких концентрациях ген Klotho обнаружен также в других органах и тканях, в частности в сердце.

Во многих исследованиях продемонстрирована протективная роль белка Klotho при кардиоваскулярной патологии. Плейотропные свойства данного белка находят свое отражение в разнообразии и взаимодействии кардиозащитных механизмов. Регуляция концентрации белка Klotho в крови и его экспрессии в клетках сердца с помощью медикаментозных средств может иметь весомое значение для клеточного метаболизма и представлять собой многообещающую мишень для лечения патологии сердца и сосудов.

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