Secretoneurin as a Novel Biomarker of Cardiovascular Episodes: Are We There Yet? A Narrative Review

Abstract

Secretoneurin (SN) is a 33 amino-acid evolutionary conserved neuropeptide from the chromogranin peptide family. SN's main effects may be cardioprotective and are believed to be mediated through its inhibition of calmodulin-dependent kinase II (CaMKII), which influences intracellular calcium handling. SN inhibition of CaMKII suppresses calcium leakage from the sarcoplasmic reticulum through the ryanodine receptor. This action may reduce the risk of ventricular arrhythmias and calcium-dependent remodelling in heart failure. SN is also involved in reducing the intracellular reactive oxygen species concentration, modulating the immune response, and regulating the cell cycle, including apoptosis. SN can predict mortality in different disease states, beyond the classical risk factors and markers of myocardial injury. Plasma SN levels are elevated soon after an arrhythmogenic episode. In summary, SN is a novel biomarker with potential in cardiovascular medicine, and probably beyond.

Keywords: CaMKII; arrhythmogenesis; cardiac arrest; heart failure; ryanodine receptor; secretoneurin.

Figure 1

Intracellular signaling pathways of secretoneurin, and biological effects. ADP—adenosine diphosphate; AMP—adenosine monophosphate; AMPK—adenosine monophosphate kinase; ATP—adenosine triphosphate; cAMP—cyclic adenosine monophosphate; CaM—calmodulin; CaMKII—calmodulin-dependent kinase II; CSQ—calsequestrin; DAG—diacylglycerol; ERK—extracellular-regulated kinase; MAPK—mitogen-associated protein kinase; MEK—MAPK/ERK kinase; OX—oxidized; SOD—superoxide dismutase; PLB—phospholamban; P—phosphorus; PKA—protein kinase A; PKC—protein kinase C; PKG—protein kinase G; PLC -phospholipase C; RAF—serine-threonine protein kinase; ROS—reactive oxygen species; SN—secretoneurin; SNR—secretoneurin receptor.

Figure 2

Calcium handling/signaling in a ventricular cardiomyocyte illustrates the potential involvement of SN in arrhythmogenic risk, heart failure, and calcium-dependent remodeling. AC—adenylyl cyclase; ADP—adenosine diphosphate; ATP - adenosine triphosphate; β-AR—beta adrenergic receptor; cAMP—cyclic adenosine monophosphate; CaMKII—calmodulin-dependent kinase II; DAD—delayed afterdepolarizations in the electrocardiogram; HF—heart failure; I_Ca,L—calcium L-type channel current; MyBP-C—myosin binding protein C1; NCX—sodium-calcium exchanger; P—phosphorus; PKA—protein kinase A; PLB—phospholamban; R—ryanodine receptor; SERCA2a—the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a; SN—secretoneurin; SR—sarcoplasmic reticulum; TnI—troponin I.