Changes of calcium cycling in HFrEF and HFpEF

Abstract

Dysfunctions of calcium cycling occur in heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF). HFrEF and HFpEF showed Ca²⁺ leakage at diastole. The compensation of Na⁺/Ca²⁺ exchanger and the decrease of T-tubule density reduces cytoplasmic Ca²⁺ concentration in HFrEF and impairs systolic function. In contrast, HFpEF has the increase of cytoplasmic Ca²⁺ concentration and diastolic dysfunctions. The decrease of mitochondrial Ca²⁺ concentration weakens myocardial contractility in HFrEF while the increased concentration retains the contractility in HFpEF. Here, the changes of calcium cycling in HFrEF and HFpEF are summarized and the possibility of relevant therapeutic targets is discussed.

Keywords: Calcium cycling; HFpEF; HFrEF; Mitochondria.

Fig. 1

Calcium cycling in HFrEF and HFpEF. Both HFrEF and HFpEF exhibit RyR2 hyperactivation and reduced SERCA2a activity, resulting in Ca²⁺ leakage during diastole. HFrEF shows increased NCX expression and decreased T-tubule density, resulting in decreased cytoplasmic Ca²⁺ during systole. In contrast, HFpEF shows decreased NCX expression and increased T-tubule density, resulting in increased cytoplasmic Ca²⁺. In the mitochondrial calcium cycling, MCU activity and MAMs content decreased in HFrEF, result in decreased mitochondrial Ca²⁺. In contrast, mitochondrial Ca²⁺ increases in HFpEF.