B-type natriuretic peptide and its role in altering Ca 2+ -regulatory proteins in heart failure—mechanistic insights

Heart failure (HF) is a worldwide disease with high levels of morbidity and mortality. The pathogenesis of HF is complicated and involves imbalances in hormone and electrolyte. B-type natriuretic peptide (BNP) has served as a biomarker of HF severity, and in recent years, it has been used to treat the disease, thanks to its cardio-protective effects, such as diuresis, natriuresis, and vasodilatation. In stage C/D HF, symptoms are severe despite elevated BNP. Disturbances in Ca 2+ homeostasis are often a dominating feature of the disease, causing Ca 2+ -regulatory protein dysfunction, including reduced expression and activity of sarcoplasmic reticulum Ca 2+ -ATPase2a (SERCA2a), impaired ryanodine receptors (RYRs) function, intensive Na + -Ca 2+ exchanger (NCX), and downregulation of S100A1. The relationship between natriuretic peptides (NPs) and Ca 2+ -regulatory proteins has been widely studied and represents important mechanisms in the etiology of HF. In this review, we present evidence that BNP may regulate Ca 2+ -regulatory proteins, in particular, suppressing SERCA2a and S100A1 expression. However, relationships between BNP and other Ca 2+ -regulatory proteins remain vague.