Serelaxin

Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats...

BACKGROUND: The therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half-life of serelaxin. Optimization of fatty acid-acetylated single-chain peptide analogues of relaxin culminated in the design and synthesis of R2R01, a potent and selective RXFP1 agonist with subcutaneous bioavailability and extended half-life. EXPERIMENTAL APPROACH: Cellular assays and pharmacological models of RXFP1 activation were used to validate the potency and selectivity of R2R01...

Serelaxin (RLX), namely the human recombinant Relaxin-2 hormone, protects the heart from ischemia/reperfusion (I/R)-induced damage due to its anti-inflammatory, anti-apoptotic and antioxidant properties. RLX acts by binding to its specific RXFP1 receptor whereby it regulates multiple transduction pathways. In this in vitro study, we offer the first evidence for the involvement of the AMP kinase/Sirtuin1 (AMPK/SIRT1) pathway in the protection by RLX against hypoxia/reoxygenation (H/R)-induced damage in H9c2 cells...

Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin-angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition...

The hormone relaxin-2 has emerged as a promising player in regulating the physiology of the cardiovascular system. Through binding to the relaxin family peptide receptor 1 (RXFP1), this hormone elicits multiple physiological responses including vasodilation induction, reduction of inflammation and oxidative stress, and angiogenesis stimulation. The role of relaxin-2, or its recombinant human form known as serelaxin, has been investigated in preclinical and clinical studies as a potential therapy for cardiovascular diseases, especially heart failure, whose current therapy is still unoptimized...

Serelaxin has an inhibitory effect on fibrosis. However, whether the anti-fibrotic effects of serelaxin are achieved by inhibiting the inflammatory response has not been clarified. This study aimed to investigate the role of serelaxin in lipopolysaccharide (LPS)-induced inflammation in cardiac fibroblasts (CFs) and elucidate the underlying mechanisms.CFs were isolated from adult rat hearts. The effect of serelaxin on the inhibition of the inflammatory response after LPS induction was examined. Cell viability was measured by MMT assay...

Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software...

BACKGROUND AND PURPOSE: Chronic heart failure, a progressive disease with limited treatment options currently available, especially in heart failure with preserved ejection fraction (HFpEF), represents an unmet medical need as well as an economic burden. The development of a novel therapeutic to slow or reverse disease progression would be highly impactful to patients and society. Relaxin-2 (relaxin) is a human hormone regulating cardiovascular, renal, and pulmonary adaptations during pregnancy...

BACKGROUND: We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes. METHODS: We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2...

Despite human recombinant H2 relaxin or serelaxin holding promise as a cardiovascular drug, its actual efficacy in chronic treatment of heart failure patients was hampered by the need to be administered by multiple daily IV injections for a long time, with obvious drawbacks in terms of patients' compliance. This in vitro study aimed at exploring the molecular background for a possible administration of the peptide hormone relaxin by the oral route. Serelaxin and purified porcine relaxin (pRLX) were subjected to simulated intestinal fluid (SIF) enzymatic digestion in vitro to mimic the behavior of gastroprotective formulations...

Relaxin, an endogenous peptide hormone, elicits vascular relaxation by its direct effect or by modulating the endothelium-dependent relaxation response and is clinically evaluated for the treatment of coronary artery disease. However, its effect on penile tissue has not been explored yet. This study aimed to investigate the effect of serelaxin, recombinant human relaxin-2, on rat corpus cavernosum (CC) under healthy and hyperglycemic conditions. Strips of CC obtained from thirty-nine male Wistar rats weighing 300-350 g were used in organ baths for isometric tension studies to investigate the serelaxin-mediated relaxation (10-12 -10-7  M) under normoglycemic conditions and the effect of serelaxin on endothelium-dependent [nitric oxide (NO)- and prostacyclin-mediated] relaxation responses under hyperglycemic conditions...

Fibrosis is a hallmark of chronic hypertension and disrupts the viability of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) post-transplantation. This study thus, determined whether the anti-fibrotic drug, serelaxin (RLX), could enhance the therapeutic effects of BM-MSCs or BM-MSC-derived exosomes (BM-MSC-EXO) in hypertensive mice. Left ventricular (LV) fibrosis in particular was assessed using conventional histological staining and non-invasive cardiac magnetic resonance imaging (CMRI). CMRI was employed using a novel magnetisation prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence to simultaneously perform late gadolinium enhancement imaging and T1 mapping...

This study is preliminary to an experiment to be performed onboard the International Space Station (ISS) and on Earth to investigate how low gravity influences the healing of sutured human skin and vein wounds. Its objective was to ascertain whether these tissue explants could be maintained to be viable ex vivo for long periods of time, mimicking the experimental conditions onboard the ISS. We developed an automated tissue culture chamber, reproducing and monitoring the physiological tensile forces over time, and a culture medium enriched with serelaxin (60 ng/mL) and (Zn(PipNONO)Cl) (28 ng/mL), known to extend viability of explanted organs for transplantation...

Cardiorenal syndrome (CRS) continues to be an area of concern due to the changing understanding of identification, pathophysiology and optimal management. Originally thought that diuretics were always the answer, recent literature has shed lights on the five major CRS subphenotypes, and while conceptual in their classifications, different strategies may be utilized to manage each type. The effect of CRS in pregnant women is largely under discussed and underappreciated as its own entity. Trials involving possible management, specifically utilizing serelaxin, a recombinant form of relaxin, have shown promising results but more data are needed to begin implementing it on a large scale...

Background: A network meta-analysis (NMA) of the current recommended drugs for the treatment of acute heart failure (AHF), was performed to compare the relative efficacy. Methods: We used PubMed, EMBASE, Cochrane Clinical Trials Register, and Web of Science systems to search studies of randomized controlled trials (RCT) for the treatment of AHF recommended by the guidelines and expert consensus until 1 December 2020. The primary outcome was all-cause mortality within 30 days. The secondary outcomes included 30-days all-cause rehospitalization, rates of HF-related rehospitalization, rates of adverse events, and rates of serious adverse events...

BACKGROUND: Recent data suggest that guideline directed medical treatment of patients with heart failure with reduced ejection fraction (HFrEF) might improve clinical outcomes in patients with heart failure (HF) up to a left ventricular ejection fraction (LVEF) of 55-65%, whereas patients with higher LVEF do not seem to benefit. Recent data have shown that LVEF may have a U-shaped relation with outcome, with poorer outcome also in patients with supranormal values. This suggests that patients with supranormal LVEF may be a distinctive group of patients METHODS AND RESULTS: RELAX AHF-2 was a multicenter, placebo-controlled trial on the effects of serelaxin on 180-day cardiovascular (CV) mortality and worsening HF at day 5 in patients with acute HF...

The peptide hormone relaxin (RLX), also available as clinical-grade recombinant protein (serelaxin), holds great promise as a cardiovascular and anti-fibrotic agent but is limited by the pharmacokinetic issues common to all peptide drugs. In this study, by a computational modelling chemistry approach, we have synthesized and tested a set of low molecular weight peptides based on the putative receptor-binding domain of the B chain of human H1 RLX isoform, with the objective to obtain RLX analogues with improved pharmacokinetic features...

Previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) is a novel yet readily evaluable inflammatory biomarker that may be useful for determining cardiovascular prognosis during acute episodes. The study investigated the role of NLR in predicting cardiovascular (CV) outcomes in patients with acute heart failure (HF). Individual patient data from the BLAST-AHF (phase 2b study of the biased ligand of the angiotensin 2 type 1 receptor, TRV027), Pre-RELAX-AHF (phase 2b study of recombinant human relaxin-2, serelaxin), and RELAX-AHF (phase 3 study of serelaxin) randomized, placebo-controlled studies for patients with acute HF were pooled for analysis...

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...

Diuretic therapy is the mainstay during episodes of acute heart failure (AHF). Diuretic resistance is often encountered and poses a substantial challenge for clinicians. There is a lack of evidence on the optimal strategies to tackle this problem. This review aimed to compare the outcomes associated with congestion management based on a strategy of pharmacological nondiuretic-based regimens. The PubMed, Cochrane Library, Scopus, and ScienceDirect databases were systematically searched for all randomised controlled trials (RCTs) of adjuvant pharmacological treatments used during hospitalisation episodes of AHF patients...