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 |
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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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