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Relaxin heart failure

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https://www.readbyqxmd.com/read/29716428/the-subset-of-patients-with-acute-heart-failure-able-to-secrete-relaxin-2-at-pregnancy-concentrations-could-have-a-longer-survival-a-pilot-study
#1
Òscar Miró, Pablo Herrero-Puente, Belén Prieto, María García-García, Pablo García-Hernández, Francisco J Martín-Sánchez, Javier Jacob, José Ríos, Rodolfo Romero, Víctor Gil, Étienne Gayat, Pere Llorens, Alexandre Mebazaa
OBJECTIVE: To investigate how many patients with acute heart failure (AHF) hypersecrete relaxin-2 concentrations similar to those of pregnant women and determine their long-term outcome. METHODS: In consecutive AHF patients relaxin-2 was quantified by ELISA sandwich method. Patients were divided into pregnancy-like group (PLG, relaxin-2 ≥ 500 pg/mL) and control group (CG, relaxin-2 < 500 pg/mL). The primary outcome was all-cause death during follow-up...
May 1, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29536410/relaxin-2-fails-to-lower-intraocular-pressure-and-to-dilate-retinal-vessels-in-rats
#2
Ulrike Hampel, Katharina Träger, Hanhan Liu, Julia Teister, Franz Grus, Verena Prokosch-Willing
PURPOSE: Recently, the vasodilator relaxin 2 has been introduced as a treatment for acute heart failure. However, its role on vessels of the eye and intraocular pressure (IOP) remains unclear though it has been hypothesized to induce a decrease IOP after intramuscular injection in humans. We aimed to test whether the hormone relaxin 2 lowers IOP and dilates retinal vessels in animals. METHODS: The IOP of female Sprague-Dawley rats before and after application of relaxin 2 was measured using an Icare Tonolab device calibrated for rats...
March 13, 2018: International Ophthalmology
https://www.readbyqxmd.com/read/29526354/heart-disease-and-relaxin-new-actions-for-an-old-hormone
#3
REVIEW
Teja Devarakonda, Fadi N Salloum
The hormone relaxin has long been recognized for its involvement in maternal adaptation during pregnancy. However, discoveries during the past two decades on the mechanism of action of relaxin, its family of receptors, and newly described roles in attenuating ischemia/reperfusion (I/R) injury, inflammation, and arrhythmias have prompted vast interest in exploring its therapeutic potential in cardiovascular disease. These observations inspired recently concluded clinical trials in patients with acute heart failure...
May 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29447958/serelaxin-as-a-novel-therapeutic-opposing-fibrosis-and-contraction-in-lung-diseases
#4
REVIEW
Maggie Lam, Simon G Royce, Chrishan S Samuel, Jane E Bourke
The most common therapies for asthma and other chronic lung diseases are anti-inflammatory agents and bronchodilators. While these drugs oppose disease symptoms, they do not reverse established structural changes in the airways and their therapeutic efficacy is reduced with increasing disease severity. The peptide hormone, relaxin, is a Relaxin Family Peptide Receptor 1 (RXFP1) receptor agonist with unique combined effects in the lung that differentiates it from these existing therapies. Relaxin has previously been reported to have cardioprotective effects in acute heart failure as well anti-fibrotic actions in several organs...
February 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29412692/the-peptide-hormone-relaxin-from-bench-to-bedside
#5
Maria Jelinic, Sarah A Marshall, Dennis Stewart, Elaine Unemori, Laura J Parry, Chen Huei Leo
The peptide hormone relaxin has numerous roles both within and independent of pregnancy and is often thought of as a 'pleiotropic hormone'. Relaxin targets several tissues throughout the body, and has many functions associated with extracellular matrix remodeling and the vasculature. This review considers the potential therapeutic applications of relaxin in cervical ripening, in vitro fertilization, preeclampsia, acute heart failure, ischemia-reperfusion and cirrhosis. We first outline the animal models used in preclinical studies to progress relaxin into clinical trials and then discuss the findings from these studies...
February 7, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29350771/recombinant-relaxin-protects-liver-transplants-from-ischemia-damage-via-hepatocyte-glucocorticoid-receptor-from-bench-to-bedside
#6
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29346407/relaxin-reverses-inflammatory-and-immune-signals-in-aged-hearts
#7
Brian Martin, Beth Ann Gabris-Weber, Rajiv Reddy, Guillermo Romero, Ansuman Chattopadhyay, Guy Salama
BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin's short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF...
2018: PloS One
https://www.readbyqxmd.com/read/29173360/combined-assessment-of-relaxin-and-b-type-natriuretic-peptide-improves-diagnostic-value-in-patients-with-congestive-heart-failure
#8
Ling Han, Jingguang Luo, Shanshan Bai, Ye Jia, Xin Chen, Yan Zhao, Liwei Chen, Xiaogang Zhu, Ying Li, Yuanyuan Jiang, Xiaohong Li, Ming Yang, Dongxia Li, Xu Teng, Yongfen Qi
BACKGROUND: To improve the poor prognosis of congestive heart failure (CHF), early and accurate diagnosis is necessary. Relaxin is an endogenous cardiovascular peptide, and its plasma level is usually increased in patients with CHF. In this pilot study, we aimed to determine the diagnostic value of relaxin and B-type natriuretic peptide (BNP) in patients with and without CHF. MATERIALS AND METHODS: The plasma level of relaxin was measured by enzyme-linked immunosorbent assay and plasma level of BNP by fluorescence immunoassay...
November 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28987540/serelaxin-inhibits-differentiation-and-fibrotic-behaviors-of-cardiac-fibroblasts-by-suppressing-alk-5-smad2-3-signaling-pathway
#9
Xue-Ping Wu, Hai-Jie Wang, Yong-Li Wang, Hao-Ran Shen, Yu-Zhen Tan
Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after induction with TGF-β1 were examined...
January 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/28978531/effects-of-serelaxin-on-renal-microcirculation-in-rats-under-control-and-high-angiotensin-environments
#10
Weijian Shao, Carla B Rosales, Camila Gonzalez, Minolfa C Prieto, L Gabriel Navar
Serelaxin is a novel recombinant human relaxin-2 that has been investigated for the treatment of acute heart failure. However, its effects on renal function, especially on the renal microcirculation, remain incompletely characterized. Our immunoexpression studies localized RXFP1 receptors on vascular smooth muscle cells and endothelial cells of afferent arterioles and on principal cells of collecting ducts. Clearance experiments were performed in male and female normotensive rats and Ang II-infused male rats...
January 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28942152/relaxin-alleviates-tgf%C3%AE-1-induced-cardiac-fibrosis-via-inhibition-of-stat3-dependent-autophagy
#11
Yue Yuan, Yun Zhang, Xuejie Han, Yanyan Li, Xinbo Zhao, Li Sheng, Yue Li
Cardiac fibrosis is a pathological feature common to a variety of heart diseases such as myocardial infarction, arrhythmias, cardiomyopathies and heart failure. Emerging data has indicted that autophagy is involved in fibrotic synthesis. Relaxin as a pleiotropic hormone can attenuate cardiac fibrosis and hypertrophy, however the exact molecular mechanism remains largely unknown. In this work, we evaluated whether the antifibrotic effect of relaxin relies on regulating autophagy in primary cardiac fibroblasts (CFs)...
December 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28868039/relaxin-2-in-cardiometabolic-diseases-mechanisms-of-action-and-future-perspectives
#12
REVIEW
Sandra Feijóo-Bandín, Alana Aragón-Herrera, Diego Rodríguez-Penas, Manuel Portolés, Esther Roselló-Lletí, Miguel Rivera, José R González-Juanatey, Francisca Lago
Despite the great effort of the medical community during the last decades, cardiovascular diseases remain the leading cause of death worldwide, increasing their prevalence every year mainly due to our new way of life. In the last years, the study of new hormones implicated in the regulation of energy metabolism and inflammation has raised a great interest among the scientific community regarding their implications in the development of cardiometabolic diseases. In this review, we will summarize the main actions of relaxin, a pleiotropic hormone that was previously suggested to improve acute heart failure and that participates in both metabolism and inflammation regulation at cardiovascular level, and will discuss its potential as future therapeutic target to prevent/reduce cardiovascular diseases...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28851937/serelaxin-improves-cardiac-and-renal-function-in-doca-salt-hypertensive-rats
#13
Dong Wang, Yuhuan Luo, Komuraiah Myakala, David J Orlicky, Evgenia Dobrinskikh, Xiaoxin Wang, Moshe Levi
Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674260/relaxin-ameliorates-renal-fibrosis-and-expression-of-endothelial-cell-transition-markers-in-rats-of-isoproterenol-induced-heart-failure
#14
Gaoshu Zheng, Jiejie Cai, Xingxing Chen, Lingzhi Chen, Wenhua Ge, Xi Zhou, Hao Zhou
There may be cardio-renal interactions in rats of isoproterenol-induced heart failure, which may be associated with renal fibrosis and endothelial-to-mesenchymal transition (EndMT). Since its discovery, relaxin (RLX) which was regarded as a reproductive hormone for a long time, is recently considered an effective antifibrotic hormone in cardiac and renal fibrosis. We studied whether RLX diminished renal fibrosis in rats of isoproterenol (Iso)-induced heart failure and investigated the mechanism. Fifty male Sprague-Dawley rats were separated into five groups for treatment: control; Iso subcutaneously injection to induce heart failure, which led to renal fibrosis; RLX subcutaneously injection at low, medium and high dose (0...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28592882/ml290-is-a-biased-allosteric-agonist-at-the-relaxin-receptor-rxfp1
#15
Martina Kocan, Mohsin Sarwar, Sheng Y Ang, Jingbo Xiao, Juan J Marugan, Mohammed A Hossain, Chao Wang, Dana S Hutchinson, Chrishan S Samuel, Alexander I Agoulnik, Ross A D Bathgate, Roger J Summers
Activation of the relaxin receptor RXFP1 has been associated with improved survival in acute heart failure. ML290 is a small molecule RXFP1 agonist with simple structure, long half-life and high stability. Here we demonstrate that ML290 is a biased agonist in human cells expressing RXFP1 with long-term beneficial actions on markers of fibrosis in human cardiac fibroblasts (HCFs). ML290 did not directly compete with orthosteric relaxin binding and did not affect binding kinetics, but did increase binding to RXFP1...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28580623/the-relationship-of-circulating-relaxin-2-concentrations-with-short-term-prognosis-in-patients-with-acute-heart-failure-the-relahf-study
#16
Pablo Herrero-Puente, Belén Prieto-García, María García-García, Pere Llorens, Francisco Javier Martín-Sánchez, Javier Jacob, Alexandre Mebazaa, Christian Mueller, Alan S Maisel, Víctor Gil, Pablo García-Hernandez, Òscar Miró
AIMS: This study aimed to determine the frequency of detectable relaxin-2 concentrations and associated factors in patients with acute heart failure (AHF) and to establish relationships with short-term outcome and clinical and analytical parameters. METHODS AND RESULTS: We performed a prospective, analytical, observational, multicentre study with cohort follow-up. We collected sociodemographic variables, previous history, basal status, previous treatment, vital signs, electrocardiographic and analytical data in the emergency department...
June 5, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28552862/imbalanced-angiogenesis-in-peripartum-cardiomyopathy%C3%A3-diagnostic-value-of-placenta-growth-factor
#17
Alexandre Mebazaa, Marie-France Seronde, Etienne Gayat, Kemi Tibazarwa, Dilly O C Anumba, Najla Akrout, Malha Sadoune, Jamela Sarb, Mattia Arrigo, Justina Motiejunaite, Said Laribi, Matthieu Legrand, Lydia Deschamps, Loubina Fazal, Lila Bouadma, Corinne Collet, Philippe Manivet, Alain Cohen Solal, Jean-Marie Launay, Jane-Lise Samuel, Karen Sliwa
BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65)...
October 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28482627/pulmonary-arterial-compliance-and-pulmonary-hemodynamic-effects-of-serelaxin-in-a-sheep-model
#18
René Schiffner, Juliane Reiche, Martin Schmidt, Christian Jung, Sebastian Walther, Andrey Irintchev, Sabine J Bischoff
BACKGROUND: The influence of the recombinant form of human relaxin-2 (serelaxin) on pulmonary hemodynamics under physiologic conditions have not been the subject of studies in an animal model up until now. METHODS: We therefore utilised the large animal model sheep, convenient in its similar cardiovascular physiology, to investigate said influence. All animals underwent right heart catheterization, a safe and reliable invasive procedure for the assessment of pulmonary hemodynamics, and then received either 30μg/kg serelaxin (n = 11) or saline (n = 13)...
2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28453725/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#19
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
Aims: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. Methods and results: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28452195/serelaxin-in-addition-to-standard-therapy-in-acute-heart-failure-rationale-and-design-of-the-relax-ahf-2-study
#20
RANDOMIZED CONTROLLED TRIAL
John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Peter S Pang, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Claudio Gimpelewicz, Leandro Boer-Martins, Margaret Wernsing, Tsushung A Hua, Thomas Severin, Marco Metra
Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular mortality by 37% through day 180...
June 2017: European Journal of Heart Failure
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