title: Acute Metabolic Influences on the Natriuretic Peptide System in Humans.
abstract: BACKGROUND
  The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress.
  
  
  OBJECTIVE
  This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms.
  
  
  METHODS
  Normotensive subjects (N = 33) were given a high-carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-κB) in the glucose-mediated effects was investigated using a NF-κB inhibitor and expression plasmids encoding NF-κB subunits.
  
  
  RESULTS
  We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-κB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-κB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells.
  
  
  CONCLUSIONS
  Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-κB signaling.
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Arora
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.|Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Connie
authors.initials: C
authors.lastname: Wu
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Tariq
authors.initials: T
authors.lastname: Hamid
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Garima
authors.initials: G
authors.lastname: Arora
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Obiajulu
authors.initials: O
authors.lastname: Agha
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Allen
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert E T
authors.initials: RET
authors.lastname: Tainsh
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.|Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Dongjian
authors.initials: D
authors.lastname: Hu
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Romy A
authors.initials: RA
authors.lastname: Ryan
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.|Harvard Stem Cell Institute, Cambridge, Massachusetts.
authors.forename: Ibrahim J
authors.initials: IJ
authors.lastname: Domian
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.|Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Bloch
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Sumanth D
authors.initials: SD
authors.lastname: Prabhu
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.|Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.|Center for Human Genetic Research, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, Tennessee.|Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University, Nashville, Tennessee.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D056945:Hep G2 Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D045265:Natriuretic Peptides / Q000096:biosynthesis / Q000235:genetics*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D011498:Protein Precursors; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*
chemical_list: C555677:MIRN425 microRNA, human; D035683:MicroRNAs; D045265:Natriuretic Peptides; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D012964:Sodium
keywords: cardiomyocyte; glucose; micro ribonucleic acid; obesity