DOCSLIB.ORG

Role of Resistin, IL-6 and NH2-Terminal Portion Probnp in The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of Resistin, IL-6 and NH2-Terminal Portion Probnp in The Cardiovascular and metabolic risk BMJ Open Diab Res Care: first published as 10.1136/bmjdrc-2020-001206 on 28 September 2020. Downloaded from Open access Original research Role of resistin, IL-6 and NH2- terminal portion proBNP in the pathogenesis of cardiac disease in type 2 diabetes mellitus Samar Ebrahim Ghanem,1 Mohamed Abdel- Samiee ,2 Mohamed Hamdy Torky,3 Ahmed Gaafar,4 Somia Mokabel Mohamed,5 Ghada Mohamed Mohamed Salah Eldin,5 Samah Mohammed Awad,6 Karema A Diab,7 Dalia M ELsabaawy,8 Sania Ali Yehia,9 Hany Abdelbary Abdelaziz Elbasyouni,10 Amr Aly Elshormilisy11 To cite: Ghanem SE, ABSTRACT Abdel- Samiee M, Torky MH, Introduction Epidemiological and genetic studies have Significance of this study et al. Role of resistin, IL-6 recorded the association between proinflammatory cytokines and NH2-terminal portion and the development of insulin resistance, diabetes, and What is already known about this subject? proBNP in the pathogenesis cardiovascular disease. The role of interleukin 6 (IL-6), NH2- ► Epidemiological and genetic studies have recorded of cardiac disease in the association between proinflammatory cytokines type 2 diabetes mellitus. terminal portion pro- brain natriuretic peptide (NT- proBNP) and resistin in the pathogenesis of heart disease in type 2 diabetes and the development of insulin resistance, diabetes, BMJ Open Diab Res Care and cardiovascular disease. 2020;8:e001206. doi:10.1136/ mellitus (T2DM) is still a matter of controversy. The current The role of interleukin 6 (IL-6), NH2-terminal por- bmjdrc-2020-001206 study aimed to evaluate the role of these biomarkers in the ► development of left ventricular systolic dysfunction and the tion pro- brain natriuretic peptide (NT- proBNP) and ability to use them as non- invasive test in the prediction of left resistin in the pathogenesis of heart disease in pa- Received 17 January 2020 ventricular hypertrophy and systolic dysfunction in T2DM. tients with type 2 diabetes mellitus is still a matter Revised 29 May 2020 Research design and methods 150 participants were of controversy. Accepted 4 August 2020 included in this case–control study. Patients were divided What are the new findings? into two subgroups according to echocardiographic findings: ► There was a significant increase in the level of re- group 1a included 46 patients with type 2 diabetes mellitus sistin, NT- proBNP and IL-6 in group 1a patients and echocardiographic evidence of abnormal systolic compared with group 1b and in healthy controls. function; group 1b included 54 patients with type 2 diabetes Echocardiographic parameters showed a significant mellitus and with normal echocardiogenic study; and group ► increase in left ventricular mass index, left ventri- 2 included 50 apparently healthy controls. Routine laboratory cle posterior wall thickness, interventricular septum investigations such as complete blood count, liver and renal thickness, and left ventricle mass in group 1a com- function tests, and lipid profile, serum IL-6, NT- proBNP, and pared with group 1b and the control group. http://drc.bmj.com/ resistin were measured in all participants. Conventional echocardiography was done with special concern on the How might these results change the focus of assessment of left ventricular systolic function (ejection research or clinical practice? fraction). ► Proinflammatory cytokines had a clear relation with Results There was a significant increase in the level of left ventricular systolic dysfunction and hypertrophy resistin, NT- proBNP and IL-6 in group 1a patients compared and can be used as early non-invasive markers for with group 1b and in healthy controls. Echocardiographic detection of left ventricular remodeling and systolic on October 2, 2021 by guest. Protected copyright. parameters showed a significant increase in left ventricular dysfunction in patients with type 2 diabetes mellitus. mass index, left ventricle posterior wall thickness, ► Resistin, NT- proBNP, IL-6 and echocardiographic interventricular septum thickness, and left ventricle mass in data and suggesting them as diagnostic markers are group 1a compared with group 1b and the control group. The a subject of great biomedical importance and con- increased left ventricular mass index was associated with tribute to knowledge. higher levels of IL-6, NT- proBNP and resistin. © Author(s) (or their Conclusions Proinflammatory cytokines had a clear relation employer(s)) 2020. Re- use permitted under CC BY-NC. No with left ventricular systolic dysfunction and hypertrophy and commercial re- use. See rights can be used as early non- invasive markers for detection of stroke, and peripheral vascular disease are the 1 and permissions. Published left ventricular remodeling and systolic dysfunction in patients main macrovascular complications of DM. by BMJ. with T2DM. Echocardiographic studies on large data- For numbered affiliations see bases of patients with diabetic heart failure end of article. INTRODUCTION have shown an association with left ventric- Correspondence to The American Heart Association designated ular hypertrophy (LVH), increased heart 2 Dr Mohamed Abdel- Samiee; diabetes mellitus (DM) as a major risk factor mass, and diastolic function. The effects of drmohammed100@ yahoo. com for cardiovascular disease (CVD). CVD, type 2 diabetes mellitus (T2DM) on the heart BMJ Open Diab Res Care 2020;8:e001206. doi:10.1136/bmjdrc-2020-001206 1 BMJ Open Diab Res Care: first published as 10.1136/bmjdrc-2020-001206 on 28 September 2020. Downloaded from Cardiovascular and metabolic risk can be broadly grouped into two main categories: coro- enrolled in the study as a control group (group 2). The nary heart disease (CHD) and diabetic cardiomyopathy source of the controls was dependent on the source of (DCM), which is characterized by LVH, left ventricular the cases, such as their family relatives. Through system- (LV) diastolic dysfunction, LV systolic dysfunction and atic random sampling, one out of five individuals from cardiac autonomic neuropathy.3 4 The common final the family relatives of the patients in group 1 was selected pathway for both CHD and DCM is clinical heart failure.5 as the control. Brain natriuretic peptide (BNP) is a potent vasodilator DM was diagnosed according to WHO and the American and a natriuretic factor regulating salt and water hemo- Diabetes Association as fasting blood glucose ≥126 mg/ stasis. It is stored in the human cardiac tissue mainly dL or 2- hour postprandial glucose (PG) ≥200 mg/dL.16 as BNP-32, with a lesser amount of the precursor pre- Inclusion criteria included adults aged more than 30 proBNP. The circulating plasma forms of BNP are BNP-32 years old and history of T2DM and on regular treatment. 6 and the NH2- terminal portion proBNP (NT-proBNP) . Exclusion criteria included pregnancy, acute coro- BNP and NT- proBNP may be used as a screening test nary syndrome, constrictive pericarditis, acute pericar- 7 for exercise- induced myocardial ischemia. In addition, ditis, hypertrophic cardiomyopathy, severe valvular heart plasma BNP in patients with systolic heart failure reflects disease, atrial fibrillation, history of chronic or acute 8 the severity of diastolic abnormality. The diagnosis of inflammatory disease in the preceding 3 months, malig- heart failure due to diastolic dysfunction is usually based nancies, autoimmune diseases, and type 1 DM. on typical symptoms and signs of heart failure in patients A written informed consent from all participants was 9 with preserved LV systolic function. taken. As vascular inflammation has emerged as an important All participants underwent the following: component of CVD, it is critical to elucidate the role of I. Full history taking and clinical examination. interleukin 6 (IL-6) in hypertension, endothelial dysfunc- 1. General examination: assessment of general con- tion,10 CHD and congestive heart failure with insulin resis- 11 dition and heart rate and blood pressure. tance in T2DM. IL-6 level increases in CVD, including 2. Cardiac examination for signs of heart failure, atherosclerosis, diabetes, heart failure, and hypertension. 12 cardiac murmurs or cardiomegaly; pulse exam- Its level is correlated positively with CVD progression. ination to detect peripheral vascular disease or Resistin is a 12.5 kD protein rich in cysteine and is 13 significant arrhythmia. produced mainly from activated white blood cells. It is 3. Anthropometric measures: measurement of a proinflammatory marker that is associated with insulin body weight in kilograms and height in meter, resistance, atherosclerosis and cardiac outcomes of DM.14 from which the body surface area (BSA) was cal- Resistin is produced and released from adipose tissue to 17 culated according to the formula of Dubois. serve endocrine functions likely involved in insulin resis- BSA(M2) = 0.007184 HEIGHT (CM)0.725 tance. This idea primarily stems from studies demon- – × × 0.425 strating that serum resistin levels increase with obesity WEIGHT (KG) and involved in energy metabolism and T2DM. Serum 4. Echocardiography. resistin levels have been found to decline with decreased The M- mode measurements obtained included the 15 following: adiposity following medical treatment. http://drc.bmj.com/ The purpose of our study was to identify the role of Two- dimensional guided M-mode measurements were these biomarkers in the development of LV systolic obtained at the left lateral position from the parasternal dysfunction and the ability to use them as a non-invasive long-axis view. Values were carefully
Load more

Recommended publications
  • The Neuroendocrine Control of Atrial Natriuretic Peptide Release J Antunes-Rodrigues1, ALV Favaretto1, J Gutkowska2 and SM Mccann3
    Molecular Psychiatry (1997) 2, 359–367 1997 Stockton Press All rights reserved 1359–4184/97 $12.00 REVIEW ARTICLE: A TRIBUTE TO SM McCANN The neuroendocrine control of atrial natriuretic peptide release J Antunes-Rodrigues1, ALV Favaretto1, J Gutkowska2 and SM McCann3 1Department of Physiology, School of Medicine, University of Sao Paulo, 14049 Ribeirao Preto, SP, Brazil; 2Laboratory of Biochemistry of Hypertension, Clinical Research Institute, University of Montreal, Montreal, Quebec, H2W 1R7 Canada; 3Pennington Biomedical Research Center (LSU), 6400 Perkins Road, Baton Rouge, LA 70808–4124, USA In the initial experiments reviewed here, we show that atrial natriuretic peptide (ANP) plays an important inhibitory role in the control of sodium chloride and water intake since injections of ANP into the third ventricle (3V) caused a reduction in dehydration-induced drinking and also the drinking of salt in salt-depleted rats. Attention was then turned to the possible role of the brain ANP neurons in producing natriuresis which had earlier been shown to be caused by stimulations within the anterior ventral third ventricular region (AV3V). Stimulation in this region by carbachol produced natriuresis accompanied by a dramatic increase in plasma ANP concentrations and increased content of the peptide in medial basal hypothalamus (MBH), neurohypophysis (NH) and anterior pituitary gland (AP), without alterations in the content of ANP in lungs or atria. This suggested that the natriuresis resulting from the stimulation is brought about, at least in part, by the release of ANP from the brain. Conversely, there was a dramatic decline in plasma ANP at both 24 and 128 h after AV3V lesions had been placed.
    [Show full text]
  • Effect of Atrial Natriuretic Peptide on the Release of 19-Endorphin from Rat Hypothalamo- Neurohypophysial Complex
    Endocrinol. Jappon. 1989,36 (5),647-653 Effect of Atrial Natriuretic Peptide on the Release of 19-Endorphin from Rat Hypothalamo- Neurohypophysial Complex YUKIHIRO IKEDA1*, ISSEI TANAKA1, YUTAKA OKI1, YOSHIO IKEDA2 AND TERUYA YOSHIMII 1Second Department of Internal Medcine, Hamamatsu Uniyersity School of Medicine, Hamamatsu 431-31 and 2Department of Neuro-Psychiatry, Fujita Gakuen Health University School of Medicine, Toyoake 470-11, Japan Abstract The aim of this study was to determine whether atrial natriuretic peptide (ANP) alters 13-endorphin (ƒÀ-END) secretion from rat intermediate pituitary and whether this effect is a direct action on the intermediate pituitary or an indirect one mediated by hypothalamic factor(s). We studied the release of β-END from rat neuro-intermediate lobes of the pituitary(NIL)and from the hypothalamo-neurohypophysial complex (HNC), which consists of the hypo- thalamus, pituitary stalk, intermediate and posterior lobes of the pituitary, by means of an in vitro perifusion system. NIL and HNC were prepared from male Wistar rats and individually perifused for 30 min with perifusion medium followed by 20 min perifusion with medium containing a-rat ANP and/or dopamine (DA). Samples of perifusion medium were collected every 5 min and subjected to RIA for n-END. The basal release of ƒÀ-END from NIL was 180% of that from HNC (p<0.01), which provides further support for the presence of hypothalamic factors that inhibit (ƒÀ-END release from the intermediate pituitary. The perifusion of HNC with ANP at 10-7 and 10-6M increased the ƒÀ-END concentration by 25 and 50%, respectively (p<0.01).
    [Show full text]
  • A Role for Natriuretic Peptides in the Central Control of Energy Balance? Kathryn E
    COMMENTARY A Role for Natriuretic Peptides in the Central Control of Energy Balance? Kathryn E. Berkseth, Ellen Schur, and Michael W. Schwartz Extending this observation, the authors also found that, like leptin, intracerebroventricular CNP activates POMC he natriuretic peptide (NP) family is comprised cells (based on induction of c-Fos) (8). These findings of atrial NP, brain NP, and c-type NP (CNP). imply a role for the melanocortin system in the effect of These peptides play diverse physiological roles CNP on food intake and, together with evidence that both T(1–5) by binding to one of two receptors: NP CNP and NPR-B are concentrated in the ARC (7), raise the receptor (NPR)-A (for atrial NP and brain NP) or NPR-B possibility that CNP-containing ARC neurons synapse onto (for CNP), both of which signal through the guanylyl and activate adjacent POMC neurons (Fig. 1B). Alterna- cyclase-cyclic GMP (cGMP) pathway (6). Among the tively, CNP neurons could conceivably activate POMC physiological systems involving NPs are those controlling cells via an indirect mechanism involving an intermediary circulating blood volume, vascular tone, electrolyte bal- neuronal subpopulation. These untested possibilities are of ance, skeletal growth, and whole-body energy expenditure interest because, although the anorectic effects of both (1–5). In addition to actions in peripheral tissues, NPs are leptin (11) and serotonin (12) involve activation of POMC present in brain (7). In the current issue of Diabetes, cells, neither leptin receptors (which signal via Janus Yamada-Goto et al. (8) report that central (but not pe- kinase–signal transducer and activator of transcription and ripheral) administration of CNP reduces food intake and phosphatidylinositol-3-kinase pathways) nor serotonin body weight.
    [Show full text]
  • Searching for Novel Peptide Hormones in the Human Genome Olivier Mirabeau
    Searching for novel peptide hormones in the human genome Olivier Mirabeau To cite this version: Olivier Mirabeau. Searching for novel peptide hormones in the human genome. Life Sciences [q-bio]. Université Montpellier II - Sciences et Techniques du Languedoc, 2008. English. tel-00340710 HAL Id: tel-00340710 https://tel.archives-ouvertes.fr/tel-00340710 Submitted on 21 Nov 2008 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE MONTPELLIER II SCIENCES ET TECHNIQUES DU LANGUEDOC THESE pour obtenir le grade de DOCTEUR DE L'UNIVERSITE MONTPELLIER II Discipline : Biologie Informatique Ecole Doctorale : Sciences chimiques et biologiques pour la santé Formation doctorale : Biologie-Santé Recherche de nouvelles hormones peptidiques codées par le génome humain par Olivier Mirabeau présentée et soutenue publiquement le 30 janvier 2008 JURY M. Hubert Vaudry Rapporteur M. Jean-Philippe Vert Rapporteur Mme Nadia Rosenthal Examinatrice M. Jean Martinez Président M. Olivier Gascuel Directeur M. Cornelius Gross Examinateur Résumé Résumé Cette thèse porte sur la découverte de gènes humains non caractérisés codant pour des précurseurs à hormones peptidiques. Les hormones peptidiques (PH) ont un rôle important dans la plupart des processus physiologiques du corps humain.
    [Show full text]
  • Elevated MR-Proanp Plasma Concentrations Are Associated With
    Yagmur et al. J Transl Med (2019) 17:415 https://doi.org/10.1186/s12967-019-02165-2 Journal of Translational Medicine RESEARCH Open Access Elevated MR-proANP plasma concentrations are associated with sepsis and predict mortality in critically ill patients Eray Yagmur1* , Johanna Hermine Sckaer2, Ger H. Koek3, Ralf Weiskirchen4 , Christian Trautwein2, Alexander Koch2† and Frank Tacke2,5† Abstract Background and aims: Mid-regional pro atrial natriuretic peptide (MR-proANP) is an established biomarker for heart failure, based on its key role in regulating homeostasis of water balance and blood pressure. The aim of the study was to determine the value of MR-proANP as a clinical biomarker in critical illness and/or sepsis. Upon admission to the medical intensive care unit (ICU), we investigated MR-proANP plasma concentrations in 217 critically ill patients (144 with sepsis, 73 without sepsis). Results were compared with 65 healthy controls. Results: MR-proANP plasma levels were signifcantly elevated in critically ill patients, when compared to healthy controls. Notably, MR-proANP levels were signifcantly higher in ICU patients with sepsis. MR-proANP levels were not associated with metabolic comorbidities like diabetes or obesity. In critically ill patients, MR-proANP plasma concen- trations correlated with infammatory cytokines, markers of organ dysfunction and several adipocytokines, such as resistin, retinol-binding protein 4 (RBP4) and adiponectin. Importantly, high MR-proANP plasma levels were associ- ated with mortality, as MR-proANP levels above 227.0 pmol/l indicated a particularly increased mortality risk in ICU patients. The association between MR-proANP and mortality was independent of single organ failure and infamma- tion markers.
    [Show full text]
  • New Anticancer Agents: Hormones Made Within the Heart
    ANTICANCER RESEARCH 32: 2515-2522 (2012) Review New Anticancer Agents: Hormones Made within the Heart DAVID L. VESELY Departments of Medicine, Molecular Pharmacology and Physiology, and Cardiac Hormone Center, James A. Haley VA Medical Center, and University of South Florida Morsani School of Medicine, Tampa, FL, U.S.A. Abstract. The heart is a sophisticated endocrine gland involved in blood pressure regulation and maintenance of synthesizing the atrial natriuretic peptide (ANP) plasma volume in animals (4-9) and humans (10-12). These prohormone which contains four peptide hormones, namely cardiac hormones, numbered by their a.a. sequences atrial natriuretic peptide, vessel dilator, kaliuretic peptide beginning at the N-terminal end of the atrial natriuretic and long-acting natriuretic peptide, which decrease up to peptide (ANP) prohormone, consist of the first 30 a.a. of the 97% of human pancreatic, breast, colon, prostate, kidney prohormone, namely, long-acting natriuretic peptide (LANP), and ovarian carcinomas, as well as small-cell and a.a. 31-67 (namely, vessel dilator), a.a. 79-98 (kaliuretic squamous cell lung cancer cells within 24 hours in cell peptide) and a.a. 99-126 (ANP) (13, 14). Each of these culture. In vivo these four cardiac hormones eliminate up to peptide hormones circulates in healthy humans, with the 80% of human pancreatic adenocarcinomas, up to two- concentrations of vessel dilator and LANP in plasma being thirds of human breast cancers, and up to 86% of human 17- to 24-fold higher than that of ANP (15-20). small-cell lung cancers in athymic mice. Their anticancer mechanism(s) target the Rat sarcoma bound guanosine Heart Hormones Eliminate up to triphosphate (RAS)-mitogen activated protein kinase kinase 97% of Cancer Cells In Vitro 1/2 (MEK1/2)-extracellular signal related kinase 1/2 (ERK1/2) kinase cascade in cancer cells.
    [Show full text]
  • LKB1/AMPK Pathway Mediates Resistin‑Induced Cardiomyocyte Hypertrophy in H9c2 Embryonic Rat Cardiomyocytes
    BIOMEDICAL REPORTS 4: 387-391, 2016 LKB1/AMPK pathway mediates resistin‑induced cardiomyocyte hypertrophy in H9c2 embryonic rat cardiomyocytes PENG LIU1, GUAN-CHANG CHENG2, QUN-HUI YE2, YONG-ZHI DENG1 and LIN WU2 1Department of Cardiovascular Surgery, The Affiliated Cardiovascular Hospital of Shanxi Medical University, and Shanxi Cardiovascular Hospital (Institute), Taiyuan, Shanxi 030024; 2Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China Received September 24, 2015; Accepted January 27, 2016 DOI: 10.3892/br.2016.593 Abstract. Resistin has been previously demonstrated to induce in cardiac hypertrophy include mitogen-activated protein cardiac hypertrophy, however, the underlying molecular kinase (MAPK), adenosine monophosphate-activated protein mechanisms of resistin-induced cardiac hypertrophy remain kinase (AMPK), transforming growth factor β (TGF-β)/smads, unclear. Using H9c2 cells, the present study investigated the Ras/Rho, janus kinase (JAK)/signal transducers and activators liver kinase B1 (LKB1)/adenosine monophosphate-activated of transcription (STAT), and calcinurin/nuclear factor of acti- protein kinase (AMPK) signaling pathway for a potential role vated T-cells (NFAT) (1,2). in mediating resistin-induced cardiomyocyte hypertrophy. LKB1 is a signaling protein (3,4) that forms a complex Treatment of H9c2 cells with resistin increased cell surface with sterile-20-related adaptor (STRAD) and mouse area, protein synthesis, and expression of hypertrophic marker protein-25 (MO25). STRAD and MO25 are required for the brain natriuretic peptide and β-myosin heavy chain. Treatment activity of LKB1 (5,6). AMPK is a substrate of LKB1, and is with metformine attenuated these effects of resistin. Further- composed of AMPKα, AMPKβ and AMPKγ subunits.
    [Show full text]
  • 60 YEARS of POMC: Biosynthesis, Trafficking, and Secretion of Pro
    56:4 N X CAWLEY and others Biosynthesis of POMC-derived 56:4 T77–T97 Thematic Review peptides 60 YEARS OF POMC Biosynthesis, trafficking, and secretion of pro-opiomelanocortin-derived peptides Correspondence should be addressed Niamh X Cawley, Zhaojin Li and Y Peng Loh to Y Peng Loh Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Email Development, National Institutes of Health, Bethesda, Maryland, USA [email protected] Abstract Pro-opiomelanocortin (POMC) is a prohormone that encodes multiple smaller peptide Key Words hormones within its structure. These peptide hormones can be generated by cleavage f hypothalamus- of POMC at basic residue cleavage sites by prohormone-converting enzymes in the pituitary-adrenal axis regulated secretory pathway (RSP) of POMC-synthesizing endocrine cells and neurons. f POMC sorting The peptides are stored inside the cells in dense-core secretory granules until released f POMC-derived peptide secretion in a stimulus-dependent manner. The complexity of the regulation of the biosynthesis, f vesicle trafficking trafficking, and secretion of POMC and its peptides reflects an impressive level of f prohormone control over many factors involved in the ultimate role of POMC-expressing cells, that processing enzymes is, to produce a range of different biologically active peptide hormones ready for action when signaled by the body. From the discovery of POMC as the precursor to adrenocorticotropic hormone (ACTH) and β-lipotropin in the late 1970s to our current Journal of Molecular Endocrinology knowledge, the understanding of POMC physiology remains a monumental body of work that has provided insight into many aspects of molecular endocrinology.
    [Show full text]
  • (BNP) in Heart Transplantation: BNP Correlation with Endomyocardial Biopsy, Laboratory and Hemodynamic Measures
    Laboratory Investigation (2004) 84, 138–145 & 2004 USCAP, Inc All rights reserved 0023-6837/04 $25.00 www.laboratoryinvestigation.org Technical Report Ventricular natriuretic peptide (BNP) in heart transplantation: BNP correlation with endomyocardial biopsy, laboratory and hemodynamic measures Isabel Herva´s1, Miguel A Arnau2, Luı´s Almenar2, Jose L Pe´rez-Pastor1, Melitina Chirivella3, Joaquı´n Osca2, Pilar Bello1, Ana Osa2, Jose F Martı´1, Francisco Vera3 and Antonio Mateo1 1Department of Nuclear Medicine; 2Department of Cardiology and 3Department of Pathology, University Hospital La Fe, Valencia, Spain A prospective study of 81 heart transplant (HT) patients was carried out in order to evaluate the evolution of brain natriuretic peptide (BNP) levels in HT patients and compare them with the degree of rejection as determined by endomyocardial biopsy. All patients were subjected to endomyocardial biopsy (532), and determination of BNP and creatinine levels as well as hemodynamic parameters. A control group of 36 volunteers was included. BNP values were significantly greater in HT patients than in healthy volunteers. In the first 3 months, BNP levels in patients with treatable rejection were significantly greater than in patients without graft rejection, although evident overlapping was observed in both distributions and discriminatory potential was low. After the third month, BNP values were similar in patients with and without rejection. Creatinine levels were observed to increase over time after transplantation, but no correlation was
    [Show full text]
  • Relaxin and Atrial Natriuretic Peptide Pathways Participate in the Anti-Fibrotic Effect of a Melon Concentrate in Spontaneously
    food & nutrition æ research ORIGINAL ARTICLE Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon concentrate in spontaneously hypertensive rats Julie Carillon1,2, Audrey Gauthier1, Sandy Barial1, Michel Tournier1, Nathalie Gayrard1, Anne-Dominique Lajoix1 and Bernard Jover1* 1EA7288 Universite´ de Montpellier, Montpellier, France; 2Bionov Research, Montpellier, France Abstract Background: In spontaneously hypertensive rats (SHR), a model of human essential hypertension, oxidative stress is involved in the development of cardiac hypertrophy and fibrosis associated with hypertension. Dietary supplementation with agents exhibiting antioxidant properties could have abeneficial effect in remodeling of the heart. We previously demonstrated a potent anti-hypertrophic effect of a specific melon (Cucumis melo L.) concentrate with antioxidant properties in spontaneously hypertensive rats. Relaxin and atrial natriuretic peptide (ANP) were reported to reduce collagen deposition and fibrosis progression in various experimental models. Objective: The aim of the present investigation was to test the hypothesis that, beside reduction in oxidative stress, the melon concentrate may act through relaxin, its receptor (relaxin/insulin-like family peptide receptor 1, RXFP1), and ANP in SHR. Design and results: The melon concentrate, given orally during 4 days, reduced cardiomyocyte size (by 25%) and totally reversed cardiac collagen content (Sirius red staining) in SHR but not in their normotensive controls. Treatment with the melon concentrate lowered cardiac nitrotyrosine-stained area (by 45%) and increased by 17Á19% the cardiac expression (Western blot) of superoxide dismutase (SOD) and glutathione peroxidase. In addition, plasma relaxin concentration was normalized while cardiac relaxin (Western blot) was lowered in treated SHR. Cardiac relaxin receptor level determined by immunohistochemical analysis increased only in treated SHR.
    [Show full text]
  • Serum Resistin Is Associated with High Risk in Patients with Congestive Heart Failure a Novel Link Between Metabolic Signals and Heart Failure
    Circ J 2007; 71: 460–464 Serum Resistin is Associated With High Risk in Patients With Congestive Heart Failure A Novel Link Between Metabolic Signals and Heart Failure Yasuchika Takeishi, MD; Takeshi Niizeki, MD; Takanori Arimoto, MD; Naoki Nozaki, MD; Osamu Hirono, MD; Joji Nitobe, MD; Tetsu Watanabe, MD; Noriaki Takabatake, MD; Isao Kubota, MD Background Resistin is derived from fat tissue in rodents, and serum levels are elevated in animal models of obesity and insulin resistance. Recent studies have reported that resistin is correlated with markers of inflamma- tion and oxidative stress and is predictive of coronary atherosclerosis in humans. However, clinical significance of serum resistin has not been examined in heart failure. Therefore, the purpose of this study was to examine whether: (1) resistin is correlated with the severity of heart failure; and (2) resistin can predict clinical outcomes of patients with heart failure. Methods and Results Serum levels of resistin in 126 patients hospitalized for heart failure and 18 control sub- jects were measured. The patients were followed up with end-points of cardiac death and re-hospitalization caused by worsening of heart failure. The serum resistin level was higher in patients with heart failure than in control subjects and increased with advancing New York Heart Association functional class. The normal upper limit of the resistin level was determined as the mean +2standard deviation value of control subjects (14.1ng/ml). In heart failure patients, the cardiac event rate was higher in patients with a high resistin level than in those with a normal level. Among age, body mass index, serum levels of resistin, brain natriuretic peptide, loop diuretics selected by the univariate Cox regression hazard analysis, age and resistin were significant predictors of future cardiac events by multivariate Cox analysis.
    [Show full text]
  • Global View of the Evolution and Diversity of Metazoan Neuropeptide Signaling
    Global view of the evolution and diversity of metazoan neuropeptide signaling Gáspár Jékely1 Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany Edited by John Gerhart, University of California, Berkeley, CA, and approved April 10, 2013 (received for review December 14, 2012) Neuropeptides are signaling molecules that commonly act via G has patterns and constraints different from the evolution of folded protein-coupled receptors (GPCRs) and are generated in neurons proteins (21). pNPs are often repetitive; the number and length by proneuropeptide (pNP) cleavage. Present in both cnidarians of repeats change during evolution, or the sequences diverge into and bilaterians, neuropeptides represent an ancient and wide- distinct peptides within a precursor (21–23). Conserved sequence spread mode of neuronal communication. Due to the inherent stretches in pNPs often constitute only a few residues corre- difficulties of analyzing highly diverse and repetitive pNPs, the sponding to biologically active short peptides (24–27). Neuro- relationships among different families are often elusive. Using peptides showing such limited conservation were nevertheless similarity-based clustering and sensitive similarity searches, I obtained shown to be ligands of orthologous GPCRs in different phyla, a global view of metazoan pNP diversity and evolution. Clustering confirming that the pNPs are orthologous (28–30). revealed a large and diffuse network of sequences connected by The high diversity and repetitive sequence of pNPs hamper significant sequence similarity encompassing one-quarter of all multiple alignment-based molecular phylogeny analyses. Al- families. pNPs belonging to this cluster were also identified in the though a pNP catalog exists (31), it is not clear how the diverse early-branching neuronless animal Trichoplax adhaerens.
    [Show full text]