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Relaxin heart failure

Raktim Kumar Ghosh, Kinjal Banerjee, Ramyashree Tummala, Somedeb Ball, Keyvan Ravakhah, Anjan Gupta
Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising health care costs and one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin-2 hormone. Relaxin was discovered in pregnancy but eventually found to have a number of other physiological actions, not only in pregnancy, but also in non-pregnant women and men...
October 11, 2016: Cardiovascular Therapeutics
Jorge Martínez Solano, Juan José Santos Mateo, Jesús Sánchez-Más, Juan Sánchez, Mari Carmen Asensio López, Domingo Pascual Figal
No abstract text is available yet for this article.
October 7, 2016: Revista Española de Cardiología
Deguo Wang, Hongjun Zhu, Qing Yang, Yirun Sun
Relaxin is safe and efficient to use for treating acute heart failure. However, the electrophysiological and arrhythmogenic effects of relaxin in an experimental healing infarction model remain unknown. In this study, a rat model with myocardial infarction (MI) received relaxin (0.5mg/kg per day) or vehicle (sodium acetate) infusion via implantable mini-pumps for 2 weeks. Thereafter, hemodynamic measurement, electrophysiological study, histological examination, and immunofluorescence labeling were performed...
September 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mariana Pintalhao, Paulo Castro-Chaves, Francisco Vasques-Novoa, Francisco Gonçalves, Luís Mendonça, Ricardo Fontes-Carvalho, Patrícia Lourenço, Pedro Almeida, Adelino Leite-Moreira, Paulo Bettencourt
AIMS: Despite the promising results of serelaxin as a new potential acute heart failure (HF) therapy, its clinical use preceded the understanding of the endogenous relaxin system in HF. We aimed to evaluate relaxin circulating levels in a population of acute HF and their association with clinical and echocardiographic parameters. METHODS AND RESULTS: We included 117 patients from a registry of acute HF. Admission serum relaxin was measured using an enzyme-linked immunosorbent assay (ELISA) kit...
August 4, 2016: European Journal of Heart Failure
Veronika Wetzl, Elisabeth Schinner, Frieder Kees, Franz Hofmann, Lothar Faerber, Jens Schlossmann
INTRODUCTION: Kidney fibrosis has shown to be ameliorated through the involvement of cyclic guanosine monophosphate (cGMP) and its dependent protein kinase I (cGKI). Serelaxin, the recombinant form of human relaxin-II, increases cGMP levels and has shown beneficial effects on kidney function in acute heart failure patients. Antifibrotic properties of serelaxin are supposed to be mediated via relaxin family peptide receptor 1 and subsequently enhanced nitric oxide/cGMP to inhibit transforming growth factor-β (TGF-β) signaling...
2016: Frontiers in Pharmacology
Javier Díez, Luis M Ruilope
Acute heart failure (AHF) is a complex clinical syndrome characterized by fluid overload and haemodynamic abnormalities (short-term clinical consequences) and the development of end-organ damage (long-term consequences). Current therapies for the treatment of AHF, such as loop diuretics and vasodilators, help to relieve haemodynamic imbalance and congestion, but have not been shown to prevent (and may even contribute to) end-organ damage, or to provide long-term clinical benefit. Serelaxin is the recombinant form of human relaxin-2, a naturally occurring hormone involved in mediating haemodynamic changes during pregnancy...
April 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Antonino Tuttolomondo, Irene Simonetta, Antonio Pinto
INTRODUCTION: Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. AREAS COVERED: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs...
July 13, 2016: Expert Opinion on Therapeutic Targets
Sabine J Bischoff, Martin Schmidt, Thomas Lehmann, Andrey Irintchev, Harald Schubert, Christian Jung, Matthias Schwab, Otmar Huber, Georg Matziolis, René Schiffner
Serelaxin, recombinant human relaxin-2, modulates endothelial vasodilatory functionality and is under evaluation for treatment of acute heart failure. Little is known about acute effects on cerebral perfusion. We tested the hypothesis that Serelaxin might also have effects on the cerebral microcirculation in a sheep model, which resembles human brain structure quite well. We used laser Doppler flowmetry and sidestream dark-field (SDF) imaging techniques, which are reliable tools to continuously assess dynamic changes in cerebral perfusion...
September 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Xin-Xin Shuai, Yi-di Meng, Yong-Xin Lu, Guan-Hua Su, Xiao-Fang Tao, Jun Han, Su-Dan Xu, Ping Luo
BACKGROUND: Relaxin is a peptide hormone which has been demonstrated to be safe and has a therapeutic effect on acute heart failure in clinic trials. However, its effect on diastolic function is still unknown. The aims of the study were to determine whether relaxin could improve the diastolic function in pressure-overloaded rat model and to analyze potential mechanisms. METHODS AND RESULTS: In the present study, a pressure-overloaded rat model induced by transaortic constriction (TAC) was established...
September 1, 2016: International Journal of Cardiology
Mohsin Sarwar, Xiao-Jun Du, Thomas B Dschietzig, Roger J Summers
The insulin-like peptide relaxin, originally identified as a hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic, angiogenic, anti-apoptotic and anti-inflammatory effects in both males and females. Relaxin produces these effects by binding to a cognate receptor RXFP1 and activating a variety of signalling pathways including cAMP, cGMP and MAPKs as well as by altering gene expression of TGF-β, MMPs, angiogenic growth factors and endothelin receptors...
May 30, 2016: British Journal of Pharmacology
Hao Zhou, Xiang Qu, Zhan Gao, Gaoshu Zheng, Jie Lin, Lan Su, Zhouqing Huang, Haiying Li, Weijian Huang
Atrial fibrillation (AF) is the most common arrhythmia requiring medical treatment and has been associated with enhanced atrial fibrosis and heart failure (HF). Relaxin (RLX), an antifibrosis and antiinflammatory peptide hormone, may be used to evaluate atrial fibrosis and is associated with HF occurrence in AF. We aimed to clarify the clinical significance of RLX level in patients with AF.We measured circulating levels of RLX and other fibrosis-related factors in 311 patients with sinus rhythm (SR; n = 116) or AF (n = 195)...
May 2016: Medicine (Baltimore)
Chen Huei Leo, Maria Jelinic, Hooi Hooi Ng, Marianne Tare, Laura J Parry
Vascular dysfunction is an important hallmark of cardiovascular disease. It is characterized by increased sensitivity to vasoconstrictors, decreases in the endothelium-derived vasodilators nitric oxide (NO) and prostacyclin (PGI2), and endothelium-derived hyperpolarization (EDH). Serelaxin (recombinant human relaxin) has gained considerable attention as a new vasoactive drug, largely through its beneficial therapeutic effects in acute heart failure. In this review we first describe the contribution of endogenous relaxin to vascular homeostasis...
June 2016: Trends in Pharmacological Sciences
Danyaal S Moin, Michelle W Bloom, Lampros Papadimitriou, Javed Butler
Outcomes for patients with acute heart failure remain suboptimal and treatments principally target improvement of symptoms. To date there has been no therapy approved for acute heart failure shown to improve mortality or readmission risk post-discharge. Serelaxin, a recombinant form of the naturally occurring polypeptide hormone relaxin, has demonstrated promise in preclinical and early clinical trials as a potentially novel therapy for acute heart failure. It is postulated through its anti-fibrotic and vasodilatory effects that this agent can improve outcomes in both the short and long term in these patients...
June 2016: Expert Review of Cardiovascular Therapy
Peter S Pang, John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Joshua Kriger, Margaret F Prescott, Tsushung A Hua, Thomas Severin, Marco Metra
OBJECTIVES: The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes. BACKGROUND: Approximately 85% of patients who present to emergency departments with acute heart failure are admitted. Identification of patients at low risk might decrease unnecessary admissions. METHODS: A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro-brain natriuretic peptide ≥1,600 ng/l to serelaxin versus placebo...
July 2016: JACC. Heart Failure
Nadine Haase, Michaela Golic, Florian Herse, Julianna Rugor, Dominik Linz, Maria Emilia Solano, Dominik N Müller, Ralf Dechend
Relaxin is a peptide related to pregnancy that induces nitric oxide-related and gelatinase-related effects, allowing vasodilation and pregnancy-related adjustments permitting parturition to occur. Relaxin controls the hemodynamic and renovascular adaptive changes that occur during pregnancy. Interest has evolved regarding relaxin and a therapeutic principle in preeclampsia and heart failure. Preeclampsia is a pregnancy disorder, featuring hypertension, proteinuria and placental anomalies. We investigated relaxin in an established transgenic rat model of preeclampsia, where the phenotype is induced by angiotensin (Ang)-II production in mid pregnancy...
2016: PloS One
Xin Hu, Courtney Myhr, Zaohua Huang, Jingbo Xiao, Elena Barnaeva, Brian A Ho, Irina U Agoulnik, Marc Ferrer, Juan J Marugan, Noel Southall, Alexander I Agoulnik
The GPCR relaxin family peptide receptor 1 (RXFP1) mediates the action of relaxin peptide hormone, including its tissue remodeling and antifibrotic effects. The peptide has a short half-life in plasma, limiting its therapeutic utility. However, small-molecule agonists of human RXFP1 can overcome this limitation and may provide a useful therapeutic approach, especially for chronic diseases such as heart failure and fibrosis. The first small-molecule agonists of RXFP1 were recently identified from a high-throughput screening, using a homogeneous cell-based cAMP assay...
March 29, 2016: Biochemistry
C H Leo, M Jelinic, H H Ng, M Tare, L J Parry
BACKGROUND AND PURPOSE: In the RELAX-AHF trial, a 48 h i.v. serelaxin infusion reduced systemic vascular resistance in patients with acute heart failure. Consistent with preclinical studies, serelaxin augments endothelial vasodilator function in rat mesenteric arteries. Little is known about the contribution of endothelium-derived relaxing factors after a longer duration of continuous serelaxin treatment. Here we have assessed vascular reactivity and mechanistic pathways in mesenteric arteries and veins and the aorta after 48 or 72 h continuous i...
March 2016: British Journal of Pharmacology
Scott P Levick, Giselle C Meléndez
No abstract text is available yet for this article.
February 1, 2016: International Journal of Cardiology
Jeremy Tietjens, John R Teerlink
Attempts at developing novel therapeutic agents for acute heart failure (AHF) over the past two decades have been marked by disappointment. Relaxin is a human peptide hormone believed to mediate many adaptive haemodynamic changes that occur during pregnancy. Because these effects may be useful for treating AHF, a recombinant version of human relaxin-2, serelaxin, has been developed as a novel therapeutic agent. Studies have confirmed serelaxin's haemodynamic effects of decreasing pulmonary and systemic resistance and increasing renal blood flow...
January 2016: Heart: Official Journal of the British Cardiac Society
V A Kumar, S S Wilson, S I Ayaz, P D Levy
Acute heart failure (AHF) is one of the most important causes of mortality, morbidity and rising healthcare costs. Despite this, there has been minimal advancement in the management of AHF and the treatment continues to focus on symptomatic improvement using vasodilators, diuretics and inotropes, none of which have shown any mortality benefits. Though originally thought of as a reproductive hormone, relaxin is now recognized as a potent vasodilator that modulates systemic and renal vascular tone, resulting in pre- and after-load reduction and a decrease in cardiac workload...
October 2015: Drugs of Today
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