New Therapeutic Approaches to the Treatment of Dyslipidemia 1: ApoC-III and ANGPTL3

Figures

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  Fig. 1. Therapeutic approaches targeting apoC-III and ANGPTL3. ASO for the inactivation of apoC-III (volanesorsen and olezarsen) and ANGPTL3 (vupanorsen), and a monoclonal antibody (evinacumab) to ANGPTL3 have been developed. ASO, antisense oligonucleotide; apoC-III, apolipoprotein C-III; ANGPTL3, angiopoietin-like protein 3.

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  Fig. 2. The role of apoC-III in triglyceride-rich lipoprotein metabolism. ApoC-III ① inhibits the interaction between LPL and TRLs, resulting in reduced lipolysis of TRLs, ② increases the synthesis and secretion of hepatic VLDL, ③ decreases hepatic clearance of TRL remnants via LDLR or LRP1 by preventing the binding of apoB and apoE to those receptors. ApoC-III, apolipoprotein C-III; LPL, lipoprotein lipase; TRL, triglyceride-rich lipoprotein; VLDL, very low-density lipoprotein; LDLR, low-density lipoprotein receptor; LRP1, LDLR-related protein 1; apoB, apolipoprotein B; apoE, apolipoprotein E; GPIHBP1, glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1; TRL-R, triglyceride-rich lipoprotein remnants.

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  Fig. 3. The role of ANGPTL3 in the metabolism of TRL (A), HDL (B), and LDL (C). ANGPTL3 inhibits LPL and EL, which are key enzymes involved in the clearance of TRL and HDL, respectively. These enzymes are also related to VLDL clearance and production of LDL, as the VLDL remnants are the precursors of LDL. By inhibiting ANGPTL3, the process drawn in a solid line is facilitated, while the process drawn in a dotted line is decreased. ANGPTL3, angiopoietin-like protein 3; TRL, triglyceride-rich proteins; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LPL, lipoprotein lipase; EL, endothelial lipase; VLDL, very low-density lipoproteins.