MiR30-GALNT1/2 axis-mediated glycosylation contributes to the increased secretion of inactive human prohormone for brain natriuretic peptide (proBNP) from failing hearts

Autor: Kosai Cho, Aoi Fujishima, Wino J. Wijnen, Kenji Kangawa, Hideyuki Kinoshita, Takao Kato, Kazuwa Nakao, Toshio Nishikimi, Yasuaki Nakagawa, Jun K. Yamashita, Motohiro Nishida, Hideaki Inazumi, Hiroyuki Okamoto, Shogo Oka, Kazuhiro Nakao, Hiroyuki Fukushima, Naoto Minamino, Koichiro Kuwahara, Takeshi Kimura, Esther E. Creemers, Takayoshi Tsutamoto
Přispěvatelé: Other departments, ACS - Amsterdam Cardiovascular Sciences, Cardiology, ACS - Heart failure & arrhythmias
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Glycosylation
Translational Studies
Prohormone
Aorta
Thoracic
030204 cardiovascular system & hematology
chemistry.chemical_compound
0302 clinical medicine
Natriuretic Peptide
Brain
Natriuretic peptide
Myocytes
Cardiac
Cells
Cultured
Original Research
microRNA
Middle Aged
Brain natriuretic peptide
Echocardiography
Chromatography
Gel
Disease Progression
N-Acetylgalactosaminyltransferases
Female
Signal transduction
Cardiology and Cardiovascular Medicine
hormones
hormone substitutes
and hormone antagonists
signal transduction
medicine.drug
medicine.medical_specialty
medicine.drug_class
Heart Ventricles
Blotting
Western
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
Secretion
cardiovascular diseases
Protein Precursors
Aged
Retrospective Studies
Heart Failure
Rats
Inbred Dahl
natriuretic peptide
business.industry
Myocardium
medicine.disease
Peptide Fragments
Rats
Disease Models
Animal
MicroRNAs
030104 developmental biology
Endocrinology
Animals
Newborn
Gene Expression Regulation
chemistry
Heart failure
business
Biomarkers
Cell Signalling/Signal Transduction
Follow-Up Studies
Zdroj: Journal of the American Heart Association, 6(2):e003601. Wiley-Blackwell
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: BackgroundRecent studies have shown that plasma levels of the biologically inactive prohormone for brain natriuretic peptide (proBNP) are increased in patients with heart failure. This can contribute to a reduction in the effectiveness of circulating BNP and exacerbate heart failure progression. The precise mechanisms governing the increase in proBNP remain unclear, however.Methods and ResultsWe used our recently developed, highly sensitive human proBNP assay system to investigate the mechanisms underlying the increase in plasma proBNP levels. We divided 53 consecutive patients hospitalized with heart failure into 2 groups based on their aortic plasma levels of immunoreactive BNP. Patients with higher levels exhibited more severe heart failure, a higher proportion of proBNP among the immunoreactive BNP forms secreted from failing hearts, and a weaker effect of BNP as estimated from the ratio of plasma cyclic guanosine monophosphate levels to log‐transformed plasma BNP levels. Glycosylation at threonines 48 and 71 of human proBNP contributed to the increased secretion of proBNP by attenuating its processing, and GalNAc‐transferase (GALNT) 1 and 2 mediated the glycosylation‐regulated increase in cardiac human proBNP secretion. Cardiac GALNT1 and 2 expression was suppressed by microRNA (miR)‐30, which is abundantly expressed in the myocardium of healthy hearts, but is suppressed in failing hearts.ConclusionsWe have elucidated a novel miR‐30‐GALNT1/2 axis whose dysregulation increases the proportion of inactive proBNP secreted by the heart and impairs the compensatory actions of BNP during the progression of heart failure.
Article
JOURNAL OF THE AMERICAN HEART ASSOCIATION. 6(2): e003601(2017)
Databáze: OpenAIRE
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