LAUSR

High-density lipoprotein (HDL) has recently been established as a novel regulator of glucose metabolism, providing therapeutic opportunities for ischaemic protection. To be clear, this mechanism is distinct from those being pursued in current trials investigating the efficacy of HDL therapies to regress and stabilize atherosclerotic plaques, including the cholesteryl ester transfer protein inhibitors. Here we highlight a potential new avenue for application of HDL therapies to support cardiac glucose metabolism and improve outcome after acute coronary syndromes. Recently published preclinical data now indicate that a single intravenous dose of reconstituted HDL (rHDL; CSL-111: human apoA-I reconstituted with phospholipids) delivered immediately post cardiac ischaemia at the onset of reperfusion rapidly increases myocardial glucose uptake. This study demonstrates that HDL directly and rapidly targets cardiac glucose metabolism via the Akt pathway at a time when glycolysis is critical for myocyte survival (Figure 1). Indeed, this intervention also reduced infarct size, enhanced remodelling and improved cardiac function two weeks after the ischaemic episode. Importantly, rHDL had similar efficacy in metabolically normal and prediabetic models. The experimental design of this study aligns with a clinical window of opportunity for HDL administration at the time of primary percutaneous intervention for acute coronary syndromes, underpinning a rationale for the use of infusible HDL therapies in this context.