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Serelaxin

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https://www.readbyqxmd.com/read/28851937/serelaxin-improves-cardiac-and-renal-function-in-doca-salt-hypertensive-rats
#1
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/28840572/pharmacologic-management-for-heart-failure-and-emerging-therapies
#2
REVIEW
Diana H Kim, Feng-Ju Chien, Howard J Eisen
PURPOSE OF REVIEW: This review aims to summarize the growing body of literature of HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) with a focus on recent pharmacologics. RECENT FINDINGS: HFrEF continues to be more widely investigated than HFpEF. Ivabradine and combinatorial treatment with sacubitril and valsartan are promising newly approved therapies. Other experimental therapies have emerged, which include Serelaxin, Empagliflozin, Neuregulin, and Omecamtive mecarbil, among others...
August 24, 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28760204/effects-of-serelaxin-on-the-outcome-of-patients-with-or-without-substantial-peripheral-edema-a-subgroup-analysis-from-the-relax-ahf-trial
#3
RANDOMIZED CONTROLLED TRIAL
Claudio Gimpelewicz, Marco Metra, John G F Cleland, Peter Szecsödy, Chuan-Chuan Chang Wun, Leandro Boer-Martins, Gad Cotter, Beth A Davison, Gary Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Peter Pang, Piotr Ponikowski, Thomas Severin, Adrian A Voors, John R Teerlink
BACKGROUND: Acute heart failure (AHF) is a heterogeneous disorder, with most of the patients presenting with breathlessness along with varying degrees of peripheral edema. The presence of peripheral edema suggests that volume overload is the cause of decompensation leading to AHF, whereas breathlessness in the absence of edema may reflect a "vascular phenotype." This analysis investigated the characteristics, therapeutic response, and outcome of patients with AHF, with and without overt peripheral edema in the RELAX-AHF trial...
August 2017: American Heart Journal
https://www.readbyqxmd.com/read/28752374/erratum-to-serelaxin-in-acute-heart-failure-patients-with-and-without-atrial-fibrillation-a-secondary-analysis-of-the-relax-ahf-trial
#4
Gerasimos Filippatos, Dimitrios Farmakis, Marco Metra, Gad Cotter, Beth A Davison, G Michael Felker, Barry H Greenberg, Tsushung A Hua, Peter S Pang, Piotr Ponikowski, Min Qian, Thomas A Severin, Adriaan A Voors, John R Teerlink
No abstract text is available yet for this article.
July 27, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28718055/early-anti-inflammatory-and-pro-angiogenic-myocardial-effects-of-intravenous-serelaxin-infusion-for-72%C3%A2-h-in-an-experimental-rat-model-of-acute-myocardial-infarction
#5
Jesus Sanchez-Mas, Antonio Lax, Mari C Asensio-Lopez, Miriam Lencina, Maria J Fernandez-Del Palacio, Angela Soriano-Filiu, Rudolf A de Boer, Domingo A Pascual-Figal
Sprague Dawley rats were subjected to acute myocardial infarction (AMI) by permanent ligation of the left anterior descending coronary artery. At the time of AMI, a subcutaneous mini-osmotic pump was implanted and animals were randomized into three groups, according to the intravenous therapy received during the first 72 h: placebo-treated (saline), serelaxin10-treated (SRLX10 = 10 μg/kg/day), or serelaxin30-treated (SRLX30 = 30 μg/kg/day). Treatment with SRLX30 reduced the expression of inflammatory cytokines and chemokines, as well as the infiltration of macrophages, and increased the expression of pro-angiogenic markers and vessel density in the infarcted myocardium after 7 days...
July 17, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28660304/differences-in-the-renal-antifibrotic-cgmp-cgki-dependent-signaling-of-serelaxin-zaprinast-and-their-combination
#6
Veronika Wetzl, Elisabeth Schinner, Frieder Kees, Lothar Faerber, Jens Schlossmann
Renal fibrosis is an important factor for end-stage renal failure. However, only few therapeutic options for its treatment are established. Zaprinast, a phosphodiesterase 5 inhibitor, and serelaxin, the recombinant form of the naturally occurring hormone relaxin, are differently acting modulators of cyclic guanosine monophosphate (cGMP) signaling. Both agents enhance cGMP availability in kidney tissue. These substances alone or in combination might interfere with the development of kidney fibrosis. Therefore, we compared the effects of combination therapy with the effects of monotherapy on renal fibrosis...
June 28, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28652653/serelaxin-increases-the-antifibrotic-action-of-rosiglitazone-in-a-model-of-hepatic-fibrosis
#7
Robert G Bennett, Ronda L Simpson, Frederick G Hamel
AIM: To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis. METHODS: Hepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone (nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry...
June 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28520449/-novelties-in-the-treatment-of-heart-failure
#8
REVIEW
Filip Souček, Jan Novak
Heart failure (HF) is a complex clinical syndrome which is manifested by characteristic symptoms and objective signs of cardiac insufficiency. The incidence of HF, particularly its chronic form, is estimated 0.4-2 % in the central and western Europe, with an increase in higher age groups, affecting 10-20 % of the population aged over 80. With respect to its growing incidence and prevalence, novel modalities of pharmacological and non-pharmacological treatment are being developed in order to improve quality of life and survival of the affected patients...
December 0: Vnitr̆ní Lékar̆ství
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
#9
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/28454809/day-vs-night-does-time-of-presentation-matter-in-acute-heart-failure-a-secondary-analysis-from-the-relax-ahf-trial
#10
RANDOMIZED CONTROLLED TRIAL
Peter S Pang, John R Teerlink, Leandro Boer-Martins, Claudio Gimpelewicz, Beth A Davison, Yi Wang, Adriaan A Voors, Thomas Severin, Piotr Ponikowski, Tsushung A Hua, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Gad Cotter, Marco Metra
BACKGROUND: Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial. METHODS: This is a post hoc analysis of the RELAX AHF trial, which randomized 1,161 AHF patients to serelaxin vs placebo, both in addition to usual AHF therapy...
May 2017: American Heart Journal
https://www.readbyqxmd.com/read/28453725/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#11
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
#12
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/28398333/top-heart-failure-contender-serelaxin-flops
#13
(no author information available yet)
No abstract text is available yet for this article.
April 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28377719/serelaxin-treatment-reduces-oxidative-stress-and-increases-aldehyde-dehydrogenase-2-to-attenuate-nitrate-tolerance
#14
Chen Huei Leo, Dhanushke T Fernando, Lillie Tran, Hooi Hooi Ng, Sarah A Marshall, Laura J Parry
Background: Glyceryl trinitrate (GTN) is a commonly prescribed treatment for acute heart failure patients. However, prolonged GTN treatment induces tolerance, largely due to increased oxidative stress and reduced aldehyde dehydrogenase-2 (ALDH-2) expression. Serelaxin has several vasoprotective properties, which include reducing oxidative stress and augmenting endothelial function. We therefore tested the hypothesis in rodents that serelaxin treatment could attenuate low-dose GTN-induced tolerance. Methods and Results: Co-incubation of mouse aortic rings ex vivo with GTN (10 μM) and serelaxin (10 nM) for 1 h, restored GTN responses, suggesting that serelaxin prevented the development of GTN tolerance...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28370794/short-term-48%C3%A2-hours-intravenous-serelaxin-infusion-has-no-effect-on-myogenic-tone-or-vascular-remodeling-in-rat-mesenteric-arteries
#15
Maria Jelinic, Chen Huei Leo, Sarah A Marshall, Sevvandi N Senadheera, Laura J Parry, Marianne Tare
BACKGROUND: Short-term IV sRLX (recombinant human relaxin-2) infusion enhances endothelium-dependent relaxation in mesenteric arteries. This is initially underpinned by increased NO followed by a transition to prostacyclin. The effects of short-term IV sRLX treatment on pressure-induced myogenic tone and vascular remodeling in these arteries are unknown. Therefore, we investigated the effects of sRLX infusion on pressure-induced myogenic tone and passive mechanical wall properties in mesenteric arteries...
August 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28245243/serelaxin-as-a-potential-treatment-for-renal-dysfunction-in-cirrhosis-preclinical-evaluation-and-results-of-a-randomized-phase-2-trial
#16
Victoria K Snowdon, Neil J Lachlan, Anna M Hoy, Patrick W F Hadoke, Scott I Semple, Dilip Patel, Will Mungall, Timothy J Kendall, Adrian Thomson, Ross J Lennen, Maurits A Jansen, Carmel M Moran, Antonella Pellicoro, Prakash Ramachandran, Isaac Shaw, Rebecca L Aucott, Thomas Severin, Rajnish Saini, Judy Pak, Denise Yates, Neelesh Dongre, Jeremy S Duffield, David J Webb, John P Iredale, Peter C Hayes, Jonathan A Fallowfield
BACKGROUND: Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28217307/worse-prognosis-of-real-world-patients-with-acute-heart-failure-from-the-czech-ahead-registry-in-comparison-to-patients-from-the-relax-ahf-trial
#17
Jindrich Spinar, Jiri Jarkovsky, Lenka Spinarova, Jiri Vitovec, Ales Linhart, Petr Widimsky, Roman Miklik, Kamil Zeman, Jan Belohlavek, Filip Malek, Cestmir Cihalik, Jiri Spac, Marian Felsoci, Petr Ostadal, Ladislav Dusek, Jiri Kettner, Jan Vaclavik, Simona Littnerova, Zdeněk Monhart, Josef Malek, Jiri Parenica
AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial...
February 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28150186/serelaxin-in-acute-heart-failure-patients-with-and-without-atrial-fibrillation-a-secondary-analysis-of-the-relax-ahf-trial
#18
Gerasimos Filippatos, Dimitrios Farmakis, Marco Metra, Gad Cotter, Beth A Davison, G Michael Felker, Barry H Greenberg, Tsushung A Hua, Peter S Pang, Piotr Ponikowski, Min Qian, Thomas A Severin, Adriaan A Voors, John R Teerlink
BACKGROUND: Atrial fibrillation (AFib) is a common comorbidity in HF and affects patients' outcome. We sought to assess the effects of serelaxin in patients with and without AFib. METHODS: In a post hoc analysis of the RELAX-AHF trial, we compared the effects of serelaxin on efficacy end points, safety end points and biomarkers in 1161 patients with and without AFib on admission electrocardiogram. RESULTS: AFib was present in 41.3% of patients...
June 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28108636/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...
January 20, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28073832/reperfusion-therapy-with-recombinant-human-relaxin-2-serelaxin-attenuates-myocardial-infarct-size-and-nlrp3-inflammasome-following-ischemia-reperfusion-injury-via-enos-dependent-mechanism
#20
Juan Valle Raleigh, Adolfo G Mauro, Teja Devarakonda, Carlo Marchetti, Jun He, Erica Kim, Scott Filippone, Anindita Das, Stefano Toldo, Antonio Abbate, Fadi N Salloum
Aims: The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin-2, serelaxin, reduces myocardial infarct size and attenuates the subsequent NLRP3 inflammasome activation leading to further loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown. Methods and results: After baseline echocardiography, adult male wild-type C57BL or eNOS knockout mice underwent myocardial infarction (MI) by coronary artery ligation for 30 min followed by 24 h reperfusion...
May 1, 2017: Cardiovascular Research
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