Related Experiment Video
Updated: Jul 9, 2025
Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Exploring apolipoprotein C-III: pathophysiological and pharmacological relevance
Chris J Packard1, Angela Pirillo2,3, Sotirios Tsimikas4
1Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Insights
Elevated triglycerides (TGs) and TG-rich lipoproteins contribute to cardiovascular risk, even with low LDL cholesterol. Targeting apolipoprotein C-III (apoC-III) offers a promising strategy for significant TG reduction and improved cardiovascular outcomes.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Pharmacology
Background:
- Despite effective LDL cholesterol reduction, residual cardiovascular risk persists.
- Elevated triglycerides (TGs) and TG-rich lipoproteins are key contributors to this residual risk.
- Apolipoprotein C-III (apoC-III) plays a critical role in regulating TG metabolism and lipoprotein clearance.
Purpose of the Study:
- To investigate the role of apolipoprotein C-III (apoC-III) in cardiovascular disease (CVD) risk.
- To evaluate novel therapeutic strategies targeting apoC-III for TG reduction.
- To assess the potential of apoC-III inhibition in managing residual cardiovascular risk.
Main Methods:
- Review of genetic studies linking APOC3 gene variants to TG levels and coronary heart disease risk.
- Analysis of current hypolipidemic drug efficacy in TG reduction.
- Examination of emerging therapeutics specifically targeting apoC-III, including antisense oligonucleotides, small interfering RNA, and monoclonal antibodies.
Main Results:
- Genetic evidence confirms a causal role for apoC-III in CVD.
- Loss-of-function mutations in APOC3 are associated with lower TGs and reduced coronary heart disease risk.
- New drugs targeting apoC-III demonstrate potential for substantial TG reductions, exceeding current therapies.
Conclusions:
- Apolipoprotein C-III is a validated therapeutic target for managing hypertriglyceridemia and reducing cardiovascular risk.
- Targeting apoC-III represents a significant advancement in addressing residual CV risk beyond LDL-C lowering.
- Novel apoC-III-targeted therapies offer a promising avenue for improved patient outcomes in cardiovascular disease prevention.
Abstract:
The availability of pharmacological approaches able to effectively reduce circulating LDL cholesterol (LDL-C) has led to a substantial reduction in the risk of atherosclerosis-related cardiovascular disease (CVD). However, a residual cardiovascular (CV) risk persists in treated individuals with optimal levels of LDL-C. Additional risk factors beyond LDL-C are involved, and among these, elevated levels of triglycerides (TGs) and TG-rich lipoproteins are causally associated with an increased CV risk. Apolipoprotein C-III (apoC-III) is a key regulator of TG metabolism and hence circulating levels through several mechanisms including the inhibition of lipoprotein lipase activity and alterations in the affinity of apoC-III-containing lipoproteins for both the hepatic receptors involved in their removal and extracellular matrix in the arterial wall. Genetic studies have clarified the role of apoC-III in humans, establishing a causal link with CVD and showing that loss-of-function mutations in the APOC3 gene are associated with reduced TG levels and reduced risk of coronary heart disease. Currently available hypolipidaemic drugs can reduce TG levels, although to a limited extent. Substantial reductions in TG levels can be obtained with new drugs that target specifically apoC-III; these include two antisense oligonucleotides, one small interfering RNA and an antibody.
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