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Relaxin heart failure

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https://www.readbyqxmd.com/read/28868039/relaxin-2-in-cardiometabolic-diseases-mechanisms-of-action-and-future-perspectives
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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)...
May 27, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28482627/improvement-of-pulmonary-arterial-compliance-and-further-pulmonary-hemodynamic-effects-of-serelaxin-in%C3%A2-a%C3%A2-sheep-model
#7
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)...
May 2, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28428753/a-clinical-perspective-of-anti-fibrotic-therapies-for-cardiovascular-disease
#10
REVIEW
Lu Fang, Andrew J Murphy, Anthony M Dart
Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28339772/heterologous-desensitization-of-cardiac-%C3%AE-adrenergic-signal-via-hormone-induced-%C3%AE-ar-arrestin-pde4-complexes
#11
Qian Shi, Minghui Li, Delphine Mika, Qin Fu, Sungjin Kim, Jason Phan, Ao Shen, Gregoire Vandecasteele, Yang K Xiang
Aims: Cardiac β-adrenergic receptor (βAR) signalling is susceptible to heterologous desensitization by different neurohormonal stimuli in clinical conditions associated with heart failure. We aim to examine the underlying mechanism of cross talk between βARs and a set of G-protein coupled receptors (GPCRs) activated by hormones/agonists. Methods and results: Rat ventricular cardiomyocytes were used to determine heterologous phosphorylation of βARs under a series of GPCR agonists...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28244195/are-circulating-relaxin-levels-related-to-pulmonary-hypertension-in-patients-with-heart-failure
#12
LETTER
Johanna E Emmens, Jozine M Ter Maaten, Adriaan A Voors
No abstract text is available yet for this article.
July 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28108636/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#13
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...
January 20, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28009437/serelaxin-in-clinical-development-past-present-and-future
#14
REVIEW
Elaine Unemori
The availability of highly purified recombinant human relaxin, serelaxin, has allowed clinical trials to be conducted in several indications and the elucidation of its pharmacology in human subjects. These studies have demonstrated that serelaxin has unique haemodynamic properties that are likely to contribute to organ protection and long-term outcome benefits in acute heart failure. Clinical observations support its consideration for therapeutic use in other patient populations, including those with chronic heart failure, coronary artery disease, portal hypertension and acute renal failure...
May 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27727514/serelaxin-in-acute-heart-failure-most-recent-update-on-clinical-and-preclinical-evidence
#15
REVIEW
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 healthcare costs and is 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 nonpregnant women and men...
February 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27726993/relaxin-concentrations-in-acute-heart-failure-patients-kinetics-and-clinical-determinants
#16
LETTER
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.
December 2016: Revista Española de Cardiología
https://www.readbyqxmd.com/read/27668534/effects-of-relaxin-on-cardiac-fibrosis-apoptosis-and-tachyarrhythmia-in-rats-with-myocardial-infarction
#17
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...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27488261/relaxin-serum-levels-in-acute-heart-failure-are-associated-with-pulmonary-hypertension-and-right-heart-overload
#18
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
https://www.readbyqxmd.com/read/27462268/involvement-of-cyclic-guanosine-monophosphate-dependent-protein-kinase-i-in-renal-antifibrotic-effects-of-serelaxin
#19
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
https://www.readbyqxmd.com/read/27418970/serelaxin-for-the-treatment-of-acute-heart-failure-a-review-with-a-focus-on-end-organ-protection
#20
REVIEW
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
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