Angiopoietin-like protein 3, or ANGPTL3, is a protein produced primarily by the liver. It plays a role in metabolic processes, particularly in how the body manages fats. This influence has made ANGPTL3 a focus of scientific research.
How ANGPTL3 Controls Fats in Your Blood
ANGPTL3 significantly influences how the body regulates lipid, or fat, metabolism. Its main function involves modulating the breakdown and storage of triglycerides and cholesterol in the bloodstream. This is achieved through its interaction with lipoprotein lipase (LPL), an enzyme that breaks down triglycerides found in circulating lipoproteins.
ANGPTL3 acts as an inhibitor of LPL activity, reducing LPL’s ability to clear triglycerides from the blood. This inhibition contributes to higher levels of triglycerides and other lipoproteins in circulation. ANGPTL3 can also form a complex with ANGPTL8, which further enhances its ability to inhibit LPL and affect the clearance of plasma triglycerides.
ANGPTL3’s Link to Cardiovascular Health
The levels of ANGPTL3 in the body have direct implications for cardiovascular health, particularly concerning conditions like atherosclerosis. Elevated levels of ANGPTL3 can lead to higher concentrations of triglycerides and low-density lipoprotein cholesterol (LDL-C) in the blood, increasing the risk for heart disease. Conversely, individuals with genetic variations, such as loss-of-function mutations in the ANGPTL3 gene, tend to have significantly lower levels of these lipids.
These genetic variations are associated with a reduced risk of coronary artery disease. For instance, heterozygous carriers of ANGPTL3 loss-of-function mutations have shown a 17% reduction in circulating triglycerides and a 12% reduction in LDL-C. This has been linked to a 34% reduction in the odds of coronary artery disease.
Targeting ANGPTL3 for Better Health
The understanding of ANGPTL3’s role in lipid metabolism has led to the exploration of therapeutic strategies aimed at inhibiting its activity. This approach is being investigated as a novel method to lower lipid levels and reduce cardiovascular risk, especially in individuals who do not adequately respond to conventional lipid-lowering treatments. Scientists are developing treatments such as monoclonal antibodies and antisense oligonucleotides to block ANGPTL3.
Monoclonal antibodies, like evinacumab, work by neutralizing ANGPTL3 levels in the bloodstream. Antisense oligonucleotides, such as vupanorsen, inhibit the production of ANGPTL3 in the liver. Clinical trials have demonstrated that these ANGPTL3-inhibiting therapies can significantly reduce plasma levels of triglycerides and LDL-C, offering a promising avenue for managing dyslipidemia.