B-type natriuretic peptide and its role in altering Ca2+-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 Ca2+ homeostasis are often a dominating feature of the disease, causing Ca2+-regulatory protein dysfunction, including reduced expression and activity of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a), impaired ryanodine receptors (RYRs) function, intensive Na+-Ca2+ exchanger (NCX), and downregulation of S100A1. The relationship between natriuretic peptides (NPs) and Ca2+-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 Ca2+-regulatory proteins, in particular, suppressing SERCA2a and S100A1 expression. However, relationships between BNP and other Ca2+-regulatory proteins remain vague.