Apolipoprotein C-II: a new look at an old protein

This editorial refers to ‘Inverse association between apolipoprotein C-II and cardiovascular mortality: role of lipoprotein lipase activity modulation’, by G. Silbernagel et al., https://doi.org/10.1093/eurheartj/ehad261. ‘I see too deep and too much’ Henri Barbusse, The Inferno (L’Enfer) With the renewed interest in triglyceride-carrying lipoproteins in atherogenesis,1 researchers are evaluating several players with roles in metabolism of these particles. The central character is lipoprotein lipase (LPL), the plasma enzyme responsible for hydrolysis of triglyceride-carrying particles such as chylomicrons and very-low-density lipoproteins (VLDLs). LPL activity reduces triglyceride levels, and both primary and secondary insufficiency of LPL leads to hypertriglyceridaemia.2 Mild to moderate hypertriglyceridaemia is associated with atherosclerotic cardiovascular disease (ASCVD), while severe hypertriglyceridaemia can predispose to acute pancreatitis, and sometimes ASCVD.3 Endothelial bound LPL requires a supporting cast of molecules that can either facilitate or impede its activity. For instance, LPL is suppressed by apolipoprotein (apo) C-III4 and angiopoietin-like protein 3 (ANGPTL3),5 while its activity is promoted by apo C-II6 and apo A-V.2 LPL function also depends on glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) and lipase mature factor 1 (LMF1).2 In this issue of the European Heart Journal, Silbernagel and colleagues focus on apo C-II.7