Liver-targeted Angptl4 silencing by antisense oligonucleotide treatment attenuates hyperlipidaemia and atherosclerosis development in APOE*3-Leiden.CETP mice.

ABSTRACT:

Aims

Angiopoietin-like 3 (ANGPTL3) and 4 (ANGPTL4) inhibit lipoprotein lipase to regulate tissue fatty acid (FA) uptake from triglyceride (TG)-rich lipoproteins such as very low density lipoproteins (VLDL). While pharmacological inhibition of ANGPTL3 is being evaluated as a lipid-lowering strategy, systemic ANGPTL4 inhibition is not pursued due to adverse effects. This study aims to compare the therapeutic potential of liver-specific Angptl3 and Angptl4 silencing to attenuate hyperlipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a well-established humanized model for lipoprotein metabolism.

Methods and results

Mice were subcutaneously injected twice per week with saline or liver-targeted antisense oligonucleotides against Angptl3, Angptl4, both, or a scr

SUBMITTER: Modder M 

PROVIDER: S-EPMC11687395 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature