Relaxin as a biological marker and therapeutic target in heart failure

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Abstract

An important task of modern cardiology is the search and study of new cardiovascular biological markers that can help in the early diagnosis of heart diseases, serve as a tool to assess the effectiveness of treatment, and act as a prognostic marker and risk stratification criterion. This literature review aimed to consider relaxin (RLN) as a new diagnostic and prognostic cardiovascular biological marker. RLN is a natural peptide hormone with a molecular weight of approximately 6000 daltons. RLN2 is the main circulating form of RLN in the blood. Although human RLN2 was originally discovered as a hormone mainly secreted by the corpus luteum of the ovary, it is also synthesized in various tissues in non-pregnant women and men and is considered one of the most pleiotropic hormones of the human body, which perform various activities beyond reproduction.

The availability of serelaxin (a recombinant molecule identical to human RLN2) has made it possible to study the effects of RLN2 on the cardiovascular system, kidneys, liver, and brain and to evaluate it in several randomized placebo-controlled clinical trials. RLN2 exerts many cardioprotective effects on the heart and vessels and has been proposed as a therapeutic target for cardiovascular diseases such as heart failure, atrial fibrillation, coronary heart disease, myocardial infarction, and arterial hypertension. Through the activation of its cognate receptor and subsequent flow of several molecular signaling pathways in the cardiovascular system, RLN2 can induce vasodilation and angiogenesis, increase arterial compliance and cardiac output, reduce vascular resistance, exert antifibrotic effects through regulation and remodeling of extracellular matrix turnover, reduce inflammation and apoptosis, inhibit oxidative stress, induce chronotropic and inotropic effects, and inhibit ventricular and atrial ectopic activity.

Further studies are needed to demonstrate the potential use of RLN as an additional laboratory tool for diagnosis, risk stratification, and prediction of cardiovascular events in patients with heart failure. The effects of relaxin on morbidity and mortality in patients with heart failure have yet to be evaluated in more detail.

About the authors

Amina M. Alieva

N.I. 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, 1 Ostrovityanova street, 117997 Moscow

Elena V. Reznik

N.I. 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, 1 Ostrovityanova street, 117997 Moscow

Irina E. Baykova

N.I. 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, 1 Ostrovityanova street, 117997 Moscow

Natalia V. Teplova

N.I. Pirogov Russian National Research Medical University

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

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

Russian Federation, 1 Ostrovityanova street, 117997 Moscow

Kira V. Voronkova

N.I. Pirogov Russian National Research Medical University

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

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

Russian Federation, 1 Ostrovityanova street, 117997 Moscow

Irina V. Kovtyukh

Scientific-Clinical Center N 2 of the Russian Research Center for Surgery named after Academician B.V. Petrovsky

Email: nurzhanna@yandex.ru
ORCID iD: 0000-0002-9176-1889
SPIN-code: 4746-3716

assistant

Russian Federation, Moscow

Nyurzhanna Kh. Khadzhieva

DNA Genetics Clinic «MedEstet»

Email: nurzhanna@yandex.ru
ORCID iD: 0000-0002-5520-281X
SPIN-code: 2520-8520

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Elena V. Surskaya

Scientific-Clinical Center N 2 of the Russian Research Center for Surgery named after Academician B.V. Petrovsky

Email: esurskaya@mail.ru
ORCID iD: 0000-0002-6847-219X
SPIN-code: 3047-8389

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Irina A. Kotikova

N.I. Pirogov Russian National Research Medical University

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

student

Russian Federation, 1 Ostrovityanova street, 117997 Moscow

Igor G. Nikitin

N.I. Pirogov Russian National Research 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, 1 Ostrovityanova street, 117997 Moscow

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2. Fig. 1. The beneficial effects of relaxin on the cardiovascular system. Here: Ang 2 — angiotensin 2; ЧСС — heart rate; α-CMA, smooth muscle cell actin; 8-OHdG, 8-hydroxy-2-deoxyguanosine-8-OH-deoxyguanosine; b-FGF, basic fibroblast growth factor; BMDEC, bone marrow-derived endothelial cells; Cx43, connexin43; ETBR, endothelin type B receptor; GPX, glutathione peroxidase; GSH, glutathione; IL-1β, interleukin-1β; IL-6, interleukin-6; LDH, lactate dehydrogenase; MCP-1, monocyte chemotactic protein-1; MDA, malondialdehyde-malonic dialdehyde; MMP, matrix metalloproteinase; NADPH, nicotinamideadenine dinucleotide phosphate; NLRP3, nucleotide-binding oligomerization domain and receptors containing leucine-rich repeats; NO, nitric oxide; NOS, nitric oxide synthase; Nrf2/HO-1, nuclear factor erythroid-2-related transcription factor/hemoxygenase 1; pAMPK, adenosine monophosphate-activated protein kinase; pAS160, phosphoactivated substrate 160 kilodalton; pERK1/2, signal-regulated protein kinases 1 and 2; PUFAs, polyunsaturated fatty acids; ROS, reactive oxygen species SOD, superoxide dismutase; SVR, systemic vascular resistance; TBAR, thiobarbituric acid; TIMP, tissue inhibitors of metalloproteinases; TNF-α, tumor necrosis factor α; VEGF, vascular endothelial growth factor; K, potassium; ↑, increase; ↓, decrease.

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