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Secretoneurin is a novel prognostic cardiovascular biomarker associated with cardiomyocyte calcium handling.
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2015 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 65, no 4, 339-51 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Secretoneurin (SN) levels are increased in patients with heart failure (HF), but whether SN provides prognostic information and influences cardiomyocyte function is unknown.

OBJECTIVES: This study sought to evaluate the merit of SN as a cardiovascular biomarker and assess effects of SN on cardiomyocyte Ca(2+) handling.

METHODS: We assessed the association between circulating SN levels and mortality in 2 patient cohorts and the functional properties of SN in experimental models.

RESULTS: In 143 patients hospitalized for acute HF, SN levels were closely associated with mortality (n = 66) during follow-up (median 776 days; hazard ratio [lnSN]: 4.63; 95% confidence interval: 1.93 to 11.11; p = 0.001 in multivariate analysis). SN reclassified patients to their correct risk strata on top of other predictors of mortality. In 155 patients with ventricular arrhythmia-induced cardiac arrest, SN levels were also associated with short-term mortality (n = 51; hazard ratio [lnSN]: 3.33; 95% confidence interval: 1.83 to 6.05; p < 0.001 in multivariate analysis). Perfusing hearts with SN yielded markedly increased myocardial levels and SN internalized into cardiomyocytes by endocytosis. Intracellularly, SN reduced Ca(2+)/calmodulin (CaM)-dependent protein kinase II δ (CaMKIIδ) activity via direct SN-CaM and SN-CaMKII binding and attenuated CaMKIIδ-dependent phosphorylation of the ryanodine receptor. SN also reduced sarcoplasmic reticulum Ca(2+) leak, augmented sarcoplasmic reticulum Ca(2+) content, increased the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions, and attenuated Ca(2+) sparks and waves in HF cardiomyocytes.

CONCLUSIONS: SN provided incremental prognostic information to established risk indices in acute HF and ventricular arrhythmia-induced cardiac arrest.

Place, publisher, year, edition, pages
2015. Vol. 65, no 4, 339-51 p.
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:uu:diva-245674DOI: 10.1016/j.jacc.2014.10.065ISI: 000348666800005PubMedID: 25634832OAI: oai:DiVA.org:uu-245674DiVA: diva2:791316
Available from: 2015-02-27 Created: 2015-02-27 Last updated: 2015-03-10Bibliographically approved

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Stridsberg, Mats
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