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.

Prognostic value of plasma secretoneurin concentration in patients with heart failure with reduced ejection fraction in one-year follow-up

“…All biological actions of SN are not yet fully understood or discovered. It is speculated that SN acts through membrane receptors [ 1 ]. It has been reported that it is a G protein-coupled receptor [ 19 ].…”

“…It is a highly conserved product of the proteolytic cleavage of the precursor protein, secretogranin II (SgII, also known as chromogranin C). SN increases in cardiac cells during myocardial dysfunction, exerting cardioprotective effects by protecting cardiomyocytes from ischemia-reperfusion injury, apoptosis, arrhythmogenesis, and myocardial remodeling [ 1 ]. SN as a potential cardiovascular marker increases its concentration in various clinical situations, providing prognostic information in the course of heart failure (HF), acute coronary syndrome, ventricular arrhythmias, cardiac surgeries, cardiac arrest, as well as in severe sepsis and septic shock [ 2–8 ].…”

“…Dysregulation of cardiomyocyte calcium metabolism is a common element in a wide range of cardiac pathologies, including HFrEF [ 5 ]. Inhibition of CaMKII by SN stops uncontrolled calcium leakage from the sarcoplasmic reticulum via the ryanodine receptor, which reduces the risk of arrhythmias and calcium-dependent remodeling in HF [ 1 ]. SN is probably upregulated as a mechanism compensating for the disturbed calcium metabolism of the cardiomyocyte due to excessive activation of CaMKII [ 1 , 6 ].…”

“…Inhibition of CaMKII by SN stops uncontrolled calcium leakage from the sarcoplasmic reticulum via the ryanodine receptor, which reduces the risk of arrhythmias and calcium-dependent remodeling in HF [ 1 ]. SN is probably upregulated as a mechanism compensating for the disturbed calcium metabolism of the cardiomyocyte due to excessive activation of CaMKII [ 1 , 6 ]. Because of the above reports and the significant role of previously used biomarkers in cardiovascular risk stratification, we decided to evaluate the prognostic value of measuring plasma SN concentration among patients with HFrEF as a predictor of unplanned hospitalization and death from all causes independently and as a composite endpoint in one-year follow-up.…”

Neuroprotective Peptides and New Strategies for Ischemic Stroke Drug Discoveries

“…Previously, we have described, in detail, medical technologies for the treatment of IS using drugs based on natural regulatory peptides [27,28,32]. Additionally, the effects of several peptides on brain impairment conditions, including NPY, substance P, galanin, nocistatin, and sectroneurin, have also been described in reviews [33][34][35]. In this review, we consider the latest achievements and trends in the development of new biologically active peptides, as well as the role of genome-wide transcriptome studies in identifying the molecular mechanisms of action of potential drugs for the development of methods for the treatment of IS.…”