In:
Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 2 ( 2017-02-02)
Abstract:
Recent studies have shown that plasma levels of the biologically inactive prohormone for brain natriuretic peptide (pro BNP ) 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 pro BNP remain unclear, however. Methods and Results We used our recently developed, highly sensitive human pro BNP assay system to investigate the mechanisms underlying the increase in plasma pro BNP 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 pro BNP 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 pro BNP contributed to the increased secretion of pro BNP by attenuating its processing, and Gal NA c‐transferase ( GALNT ) 1 and 2 mediated the glycosylation‐regulated increase in cardiac human pro BNP secretion. Cardiac GALNT 1 and 2 expression was suppressed by micro RNA (miR)‐30, which is abundantly expressed in the myocardium of healthy hearts, but is suppressed in failing hearts. Conclusions We have elucidated a novel miR‐30‐ GALNT 1/2 axis whose dysregulation increases the proportion of inactive pro BNP secreted by the heart and impairs the compensatory actions of BNP during the progression of heart failure.
Type of Medium:
Online Resource
ISSN:
2047-9980
DOI:
10.1161/JAHA.116.003601
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
2653953-6
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