Secretoneurin Is a Novel Prognostic Cardiovascular Biomarker Associated With Cardiomyocyte Calcium Handling
Anett Hellebø Ottesen, William E. Louch, Cathrine R. Carlson, Ole J.B. Landsverk, Jouni Kurola, Rune Forstrøm Johansen, Morten K. Moe, Jan Magnus Aronsen, Arne Didrik Høiseth, Hilde Jarstadmarken, Ståle Nygård, Magnar Bjørås, Ivar Sjaastad, Ville Pettilä, Mats Stridsberg, Torbjørn Omland, Geir Christensen and Helge Røsjø
(A) As a biomarker, secretoneurin (SN) levels stratify mortality risk at hospital admission for patients with acute heart failure (p < 0.001 by the log-rank test for SN quartiles [Q]). (B) Experimental studies of SN in isolated cells and explanted hearts demonstrate that (1.) SN is internalized into cardiomyocytes and the intact heart by endocytosis. (2.) SN binds directly to calmodulin (CaM) and CaM-dependent protein kinase II δ (CaMKIIδ), and inhibits CaMKIIδ activity. (3.) This leads to reduced Ser2814-ryanodine receptor 2 (RyR2) phosphorylation, and (4.) improved Ca2+ homeostasis.