Fibroblast growth factor 21 as a new tool in the multicomponent assessment of cardiovascular diseases

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Abstract

Currently, the search and study of new biological markers that can assist in the early diagnosis of cardiovascular diseases, serving as a laboratory tool for assessing the efficiency of ongoing therapy and being a prognostic criterion of possible clinical outcomes and a significant indicator in risk stratification, remain relevant. Two decades have passed since fibroblast growth factor 21 (FGF21), the 21st member of the FGF family, was identified and cloned. FGF21 is a secreted protein that acts as a metabolic regulator and participates in glucose homeostasis, ketogenesis, and regulation of insulin sensitivity. FGF21 expression is controlled by PPAR alpha receptor, which activates peroxisome proliferation. The liver is the main site of FGF21 production. Extrahepatic tissues such as white adipose tissue, brown adipose tissue, and skeletal muscle also express FGF21. Human FGF21 contains 209 amino acids, whereas the mouse counterpart has 210. Mouse and human FGF21 have 75% homology. Endocrine actions of FGF21 include enhancing glucose uptake by adipocytes of white adipose tissue via a unidirectional glucose transporter protein and activating the thermogenic function of brown adipose tissue. Furthermore, FGF21 has autocrine/paracrine effects, such as the induction of hepatic ketogenesis. FGF21 affects target cells with the participation of FGFR1 and FGFR4 receptors and beta-Klotho, a single-pass transmembrane protein that functions as an obligate cofactor of FGF21 signaling. Animal studies have clearly demonstrated that FGF21 acts directly on cardiac tissue, preventing the development of cardiac hypertrophy and reducing post-infarction damage and diabetic cardiomyopathy. Accumulating data emphasize the value of FGF21 as a new biological marker for diagnosis and prognosis assessment in patients with cardiac issues. Moreover, the role of FGF21 in heart diseases is very interesting because of its cardioprotective effects. Future large-scale prospective studies are necessary to confirm of the diagnostic, predictive, and possibly therapeutic role of this marker.

About the authors

Amina M. Alieva

Pirogov Russian National Research Medical University

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

MD, Cand. Sci. (Med.), assistant professor

Russian Federation, Moscow

Irina E. Baikova

Pirogov Russian National Research Medical University

Email: 1498553@mail.ru
ORCID iD: 0000-0003-0886-6290
SPIN-code: 3054-8884

MD, Cand. Sci. (Med.), assistant professor

Russian Federation, Moscow

Elena V. Reznik

Pirogov Russian National Research Medical University

Email: elenaresnik@gmail.com
ORCID iD: 0000-0001-7479-418X
SPIN-code: 3494-9080
ResearcherId: N-6856-2016

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

Russian Federation, Moscow

Ramiz K. Valiev

Loginov Moscow Clinical Scientific and Practical Center

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

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Islam Z. Akhmatov

Razumovsky Saratov State Medical University of the Ministry of Health of Russia

Email: ballard@internet.ru
Russian Federation, Saratov

Roza A. Arakelyan

Pirogov Russian National Research Medical University

Email: Elmira.sharm@yandex.ru
ORCID iD: 0000-0002-2500-197X
Russian Federation, Moscow

Mukhammetsakhet N. Saryev

Loginov Moscow Clinical Scientific and Practical Center

Email: mishamoff@gmail.com
ORCID iD: 0000-0003-1794-9258
Russian Federation, Moscow

Igor G. Nikitin

Pirogov Russian National Research Medical University

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

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

Russian Federation, Moscow

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2. Fig. 1. Intracellular mechanisms involved in the control of FGF21 production and its effects on the heart [3].1, cardiac pathology; 2, blood flow; 3, stress; 4, fatty acid metabolism; 5, apoptosis; 6, reactive oxygen species.

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3. Fig. 2. Main properties of FGF21.1, heart; 2, liver; 3, myocardial infarction; 4, oxidative stress; 5, endoplasmic reticulum stress; 6, diabetic cardiomyopathy; 7, mitochondrial dysfunction; 8, myocardial ischemia; 9, white adipose tissue; 10, brown adipose tissue; 11, proinflammatory stimuli; 12, hypertrophic stimuli; 13, blood flow; 14, endocrine activity; 15, auto/paracrine activity.

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Copyright (c) 2022 Alieva A.M., Baikova I.E., Reznik E.V., Valiev R.K., Akhmatov I.Z., Arakelyan R.A., Saryev M.N., Nikitin I.G.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


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