Fig. 2.

Angiopoietin-like protein 3 (ANGPTL3) inhibition lowers LDL-cholesterol. Schematic depicting the mechanism whereby ANGPTL3 inhibition lowers LDL-cholesterol. Upper panel: During homeostasis, ANGPTL3 diminishes the activity of vascular lipases lipoprotein lipase (LPL) and endothelial lipase (EL) and regulates APOB-containing lipoprotein turnover. Lower panel: Evinacumab unblocks the inhibitory effect of ANGPLT3 on both lipases, promoting VLDL remodeling and preferential removal of VLDL remnants from the circulation by hepatic remnant receptors, and reducing the pool for LDL. Thus, ANGPTL3 inhibition with a fully human monoclonal antibody lowers LDL-cholesterol by diminishing vascular LDL production. The effect of evinacumab on Apo B secretion require further study. APOB, apolipoprotein B.