Targeting calcium transport in ischaemic heart disease

Abstract

Ischaemic heart disease (IHD) is the leading cause of morbidity and mortality worldwide. While timely reperfusion of acutely ischaemic myocardium is essential for myocardial salvage, it leads to a unique type of injury known as 'myocardial ischaemia/reperfusion (I/R) injury'. Growing evidence suggests that a defect in myocardial Ca(2+) transport system with cytosolic Ca(2+) overload is a major contributor to myocardial I/R injury. Progress in molecular genetics and medicine in past years has clearly demonstrated that modulation of Ca(2+) handling pathways in IHD could be cardioprotective. The potential benefits of these strategies in limiting I/R injury are vast, and the time is right for challenging in vivo systemic work both at pre-clinical and clinical levels.

Figure 1

Strategies to modulate Ca²⁺ transport in the post-ischaemic heart. The primary targets to modulate Ca²⁺ overload and improve post-ischaemic myocardial performance are (i) Sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA), (ii) Na⁺/Ca²⁺ exchanger (NCX), (iii) SR Ca²⁺ release channel RyR, (iv) L-type Ca²⁺ channel (LTCC), (v) Na⁺–H⁺ exchanger (NHE), and (vi) Ca²⁺ and calmodulin-dependent protein kinase II (CaMKII).