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ANGPTL3 as therapeutic target
1Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, the Netherlands.
Purpose Of Review:
Elevated LDL-C and triglycerides are important risk factors for the development of atherosclerotic cardiovascular disease. Although effective therapies for lipid lowering exist, many people do not reach their treatment targets. In the last two decades, ANGPTL3 has emerged as a novel therapeutic target for lowering plasma LDL-C and triglycerides. Here, an overview of the recent literature on ANGPTL3 is provided, focusing on the therapeutic benefits of inactivation of ANGPTL3 via monoclonal antibodies, antisense oligonucleotides, and other more nascent approaches. In addition, the potential mechanisms by which ANGPTL3 inactivation lowers plasma LDL-C are discussed.
Recent Findings:
ANGPTL3 is a factor secreted by the liver that inhibits lipoprotein lipase and other lipases via the formation of a complex with the related protein ANGPTL8. Large-scale genetic studies in humans have shown that carriers of loss-of-function variants in ANGPTL3 have lower plasma LDL-C and triglyceride levels, and are at reduced risk of atherosclerotic cardiovascular disease. Clinical studies in patients with different forms of dyslipidemia have demonstrated that inactivation of ANGPTL3 using monoclonal antibodies or antisense oligonucleotides markedly lowers plasma LDL-C and triglyceride levels.
Summary:
Anti-ANGPTL3 therapies hold considerable promise for reducing plasma LDL-C and triglycerides in selected patient groups.
Insights
Inactivating ANGPTL3, a key factor in lipid metabolism, effectively lowers LDL-C and triglycerides. This offers a promising new approach for managing atherosclerotic cardiovascular disease risk.
Area of Science:
- Biochemistry
- Genetics
- Cardiology
Background:
- Elevated LDL-C and triglycerides are significant risk factors for atherosclerotic cardiovascular disease.
- Current lipid-lowering therapies often fail to achieve target levels for many patients.
- ANGPTL3 has emerged as a novel therapeutic target for managing dyslipidemia.
Purpose of the Study:
- To provide an overview of recent literature on ANGPTL3.
- To focus on the therapeutic benefits of ANGPTL3 inactivation.
- To discuss potential mechanisms of ANGPTL3's lipid-lowering effects.
Main Methods:
- Review of recent literature on ANGPTL3.
- Focus on therapeutic benefits of ANGPTL3 inactivation via monoclonal antibodies and antisense oligonucleotides.
- Discussion of emerging therapeutic approaches targeting ANGPTL3.
Main Results:
- ANGPTL3, secreted by the liver, inhibits lipases by complexing with ANGPTL8.
- Loss-of-function variants in ANGPTL3 are associated with lower LDL-C, triglycerides, and reduced cardiovascular risk.
- Clinical studies show ANGPTL3 inactivation significantly lowers LDL-C and triglycerides in dyslipidemia patients.
Conclusions:
- Anti-ANGPTL3 therapies demonstrate significant potential for reducing LDL-C and triglycerides.
- These therapies are promising for selected patient groups with dyslipidemia.
- Targeting ANGPTL3 represents a novel strategy in cardiovascular disease prevention.
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