Relaxin-2 as a Potential Biomarker in Cardiovascular Diseases

Abstract

The pleiotropic hormone relaxin-2 plays a pivotal role in the physiology and pathology of the cardiovascular system. Relaxin-2 exerts relevant regulatory functions in cardiovascular tissues through the specific receptor relaxin family peptide receptor 1 (RXFP1) in the regulation of cardiac metabolism; the induction of vasodilatation; the reversion of fibrosis and hypertrophy; the reduction of inflammation, oxidative stress, and apoptosis; and the stimulation of angiogenesis, with inotropic and chronotropic effects as well. Recent preclinical and clinical outcomes have encouraged the potential use of relaxin-2 (or its recombinant form, known as serelaxin) as a therapeutic strategy during cardiac injury and/or in patients suffering from different cardiovascular disarrangements, especially heart failure. Furthermore, relaxin-2 has been proposed as a promising biomarker of cardiovascular health and disease. In this review, we emphasize the relevance of the endogenous hormone relaxin-2 as a useful diagnostic biomarker in different backgrounds of cardiovascular pathology, such as heart failure, atrial fibrillation, myocardial infarction, ischemic heart disease, aortic valve disease, hypertension, and atherosclerosis, which could be relevant in daily clinical practice and could contribute to comprehending the specific role of relaxin-2 in cardiovascular diseases.

Keywords: biomarker; cardiac; cardiovascular disease; heart; relaxin; relaxin-2.

Figure 1

Relaxin-2’s beneficial effects on the heart and the vasculature. Through its cognate receptor relaxin family peptide receptor 1 (RXFP1), relaxin-2 is able to induce a myriad of cardioprotective roles [33,34,39,40]. α-SMA: α-smooth muscle actin. 8-OHdG: 8-hydroxy-2-deoxyguanosine. b-FGF: basic-fibroblast growth factor. BMDEC: bone marrow-derived endothelial cells. Cx43: connexin43. ECM: extracellular matrix. ET_BR: endothelin B receptor. GPX: glutathione peroxidase. GSH: glutathione. IL-1β: interleukin-1β. IL-6: interleukin-6. LDH: lactate dehydrogenase. MCP-1: monocyte chemoattractant protein-1. MDA: malondialdehyde. MMP: matrix metalloproteinase. NADPH: nicotinamide-adenine-dinucleotide phosphate. NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domains-containing protein 3. NO: nitric oxide. NOS: nitric oxide synthase. Nrf2/HO-1: nuclear factor erythroid 2-related factor transcription factor/hemoxygenase 1. pAMPK: phospho-adenosine monophosphate-activated protein kinase. pAS160: phospho-Akt substrate of 160 kDa. pERK1/2: phospho-extracellular signal-regulated protein kinases 1 and 2. PUFAs: polyunsaturated fatty acids. ROS: reactive oxygen species. RXFP1: relaxin family peptide receptor 1. SOD: superoxide dismutase. SVR: systemic vascular resistance. TBARs: thiobarbituric acid-reactive substance. TIMP: tissue inhibitor of metalloproteinase. TNF-α: tumour necrosis factor-α. VEGF: vascular endothelial growth factor. ↑: increase. ↓: decrease. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/ (accessed on 1 May 2022)).

Figure 2

Effects mediated by relaxin-2 (or serelaxin) that counteract end-organ damage and improve haemodynamic imbalance during heart failure [12,15,33,95]. Ang II: angiotensin II. DBP: diastolic blood pressure. I-R: ischemia-reperfusion. MDA: malondialdehyde. NT-proBNP: N-terminal pro-B-type natriuretic peptide. PAP: pulmonary artery pressure. JVP: jugular venous pressure. PCWP: pulmonary capillary wedge pressure. SBP: systolic blood pressure. SVR: systemic vascular resistance. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/ (accessed on 1 May 2022)).