Relaxin-2 plasma levels in atrial fibrillation are linked to inflammation and oxidative stress markers

Abstract

Relaxin-2 exerts many favourable cardiovascular effects in pathological circumstances such as atrial fibrillation (AF) and heart failure, but the mechanisms underlying its actions are not completely understood. Since inflammation and fibrosis are pivotal processes in the pathogenesis of AF, our aim was to study the relationship between relaxin-2 plasma levels in left atrium (LA) and peripheral vein with molecules implicated in fibrosis, inflammation and oxidative stress in AF patients, and to evaluate the anti-fibrotic ability of relaxin-2 in normal human atrial cardiac fibroblasts (NHCF-A). Peripheral vein relaxin-2 plasma levels were higher than LA relaxin-2 plasma levels in men while, in women, peripheral vein relaxin-2 levels were increased compared to men. AF patients with higher levels of relaxin-2 exhibited a reduction in H2O2 plasma levels and in mRNA levels of alpha-defensin 3 (DEFA3) and IL-6 in leucocytes from LA plasma. Relaxin-2-in-vitro treatment inhibited NHCF-A migration and decreased mRNA and protein levels of the pro-fibrotic molecule transforming growth factor-β1 (TGF-β1). Our results support an association between relaxin-2 and molecules involved in fibrosis, inflammation and oxidative stress in AF patients, and reinforce an anti-fibrotic protective role of this hormone in NHCF-A; strengthening the relevance of relaxin-2 in AF physiopathology, diagnosis and treatment.

Developing Pharmacological Therapies for Atrial Fibrillation Targeting Mitochondrial Dysfunction and Oxidative Stress: A Scoping Review

“…Elevated levels of relaxin-2 are associated with reduced expression of inflammatory markers, hydrogen peroxide concentration, inflammation, and OS genes. In vitro, treatment with relaxin-2 has demonstrated its ability to inhibit the migration of atrial heart fibroblasts and reduce the expression of profibrotic molecules [ 42 ].…”

Metabolomics and Biomarkers for Paroxysmal and Persistent Atrial Fibrillation

“…Previous studies have linked inflammation and oxidative stress to the pathophysiology of AF. 23 In the KEGG analyses, both glycolic acid and l ‐serine are linked with the carbon metabolism and glyoxylate and dicarboxylate metabolic pathways that are associated with AF (Figure 5 ). Glycolic acid is highly associated with xanthine, which is related to oxidative stress.…”

Predisposing and Overall Effects of Reproductive Hormones on Breast Cancer: A Review

“…A class of peptide hormone/neuromodulators known as relaxins (RLNs) can control various physiological functions, including brain function and reproduction [ 16 ]. In pathological conditions like AF (atrial fibrillation) and cardiac failure, relaxin-2 has several beneficial cardiovascular benefits, although the exact processes by which it works are still poorly known [ 17 ]. Relaxin-2 plays a crucial function in many malignancies, as evidenced by the pro- and antitumor effects observed in various malignant tumors.…”