Liver-targeted Angptl4 silencing reduces high cholesterol and atherosclerosis in mice
Author Information
Author(s): Melanie Modder, Wietse In het Panhuis, Mohan Li, Salwa Afkir, Alexandra L Dorn, Amanda C M Pronk, Trea C M Streefland, Reshma A Lalai, Stefan Pierrou, Stefan K Nilsson, Gunilla Olivecrona, Sander Kooijman, Patrick C N Rensen, Milena Schönke
Primary Institution: Leiden University Medical Center
Hypothesis
Can liver-specific silencing of Angptl3 and Angptl4 reduce hyperlipidemia and atherosclerosis development in mice?
Conclusion
Liver-targeted Angptl4 silencing significantly lowers cholesterol and atherosclerosis development in mice without adverse effects.
Supporting Evidence
- Liver-targeted Angptl4 silencing reduced plasma triglycerides by 48% and total cholesterol by 56%.
- Angptl4 silencing decreased atherosclerotic lesion size by 86%.
- Combined Angptl3/4 silencing lowered plasma triglycerides independent of nutritional state.
- Anti-ANGPTL4 ASO treatment was well tolerated in cynomolgus monkeys without adverse effects.
Takeaway
This study shows that targeting a specific protein in the liver can help lower bad fats in the blood and prevent heart disease in mice.
Methodology
Mice were treated with liver-targeted antisense oligonucleotides to silence Angptl3 and Angptl4, and their plasma lipid levels and atherosclerosis development were assessed.
Potential Biases
Potential conflicts of interest due to funding from Lipigon Pharmaceuticals.
Limitations
The study was conducted in mice, and results may not directly translate to humans.
Participant Demographics
Female APOE*3-Leiden.CETP mice aged 8–14 weeks.
Statistical Information
P-Value
p<0.001
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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