Lipoprotein(a) in clinical practice: From genetic risk assessment to therapeutic silencing

Figure 1 Schematic representation of the structural organization of lipoprotein(a). LDL: Low-density lipoprotein; ApoB-100: Apolipoprotein B-100; KIV: Kringle IV.

Figure 2 Schematic representation of the pro-atherogenic and pro-thrombotic mechanisms associated with elevated lipoprotein(a), highlighting the role of smaller apolipoprotein(a) isoforms with fewer kringle IV type 2 repeats in promoting atherosclerosis and thrombosis. apo(a): Apolipoprotein(a); KIV-2: Kringle IV type 2; Lp(a): Lipoprotein(a); MCP-1: Monocyte chemotactic protein-1; OxPL: Oxidized phospholipids.

Figure 3 Schematic representation of the mechanisms of action of GalNAc-conjugated therapies targeting lipoprotein(a) gene expression, reducing apolipoprotein(a) synthesis and circulating lipoprotein(a) levels through messenger RNA degradation. A: N-acetylgalactosamine-asialoglycoprotein receptor-mediated hepatocyte uptake; B: RNase H-mediated apolipoprotein(a) [apo(a)] mRNA degradation by pelacarsen; C: RNA-induced silencing complex-mediated apo(a) mRNA degradation by siRNAs; D: Translation of apo(a) mRNA into apo(a) protein. GalNAc: N-acetylgalactosamine; ASGPR: Asialoglycoprotein receptor; RISC: RNA-induced silencing complex; RNase H: Ribonuclease H; apo(a): Apolipoprotein(a).