Apolipoprotein C-III: Going Back to the Future for a Lipid Drug Target
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Importance of Apo C-III From GeneticsGenetic studies in humans and in animal model systems confirm the central role of apo C-III in lipoprotein metabolism and vascular biology.The APOC3 gene resides within the important APOA5-APOA4-APOC3-APOA1 multigene cluster on human chromosome 11q23.This locus produces the strongest association signal in genome-wide association studies of plasma TG concentration, 21,22 although there is some ambiguity about the particular genes and variants that underlie this signal.Although APOC3 was historically considered the strongest candidate gene locus associated with plasma TG concentration, 22 the Global Lipids Genetics Consortium investigators and others working with genomewide association studies have more recently designated Apolipoprotein C-III Going Back to the Future for a Lipid Drug Target
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Apo C-III has net deleterious effects on lipoprotein metabolism.
“Apo C-III is expressed both intestinally and hepatically, circulates with TG-rich lipoproteins, has net deleterious effects on lipoprotein metabolism58–63”
From Clinical review on triglycerides (2020) · cites this paper as [59]
The combination of ApoB greater than 120 mg/dL and triglycerides greater than 1.5 mmol/L with a family history of premature cardiovascular disease can identify people who most probably have familial combined hyperlipidaemia.
“the combination of ApoB > 120 mg/dL and TGs > 1.5 mmoL/ L (> 133 mg/dL) with a family history of premature CVD can be used to identify people who most probably have FCH [360].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [360]
A gain-of-function mutation in apoC3 that raises apoC3 levels can cause severe HTG by inhibiting LPL activity.
“A gain of function mutation in apoC3 leading to high apoC3 levels can also cause severe HTG by the inhibition of LPL activity”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [306]
Loss-of-function mutations in apoC3 are associated with a favourable lipid profile and low TG levels.
“whereas loss of function mutations are associated with a favourable lipid profile with low TG levels. 306”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [306]
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Isotopic Tracers for the Measurement of Metabolic Flux Rates
Beysen, C., Hellerstein, M. K., & Turner, S. (2014) · Springer eBooks · doi:10.1007/978-1-4471-4920-0_3 · Cited by 4 · see citing works
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A very rare case of chylomicronemia revealed by cerebral thrombophlebitis in a 4-month-old infant
Es-Saad, O., Lamzouri, O., Bouchlarhem, A., Haddar, L., Aabdi, M., Mimouni, H., zerouati, K., Bkiyar, H., & Housni, B. (2022) · Annals of Medicine and Surgery · doi:10.1016/j.amsu.2022.103276 · Cited by 3 · see citing works
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Investigated treatments for lipoprotein lipase deficiency and related metabolic disorders
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Isotopic Tracers for the Measurement of Metabolic Flux Rates
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Is apoCIII-Lowering A Double-Edged Sword?
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Apolipoproteins and cardiovascular diseases
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Additional file 1 of Burden of Mendelian disorders in a large Middle Eastern biobank
Aamer, W., Al-Maraghi, A., Syed, N., Gandhi, G. D., ALIYEV, E. E., Al-Kurbi, A. A., Al-Saei, O., Kohailan, M., Krishnamoorthy, N., Palaniswamy, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25560873
Additional file 2 of Burden of Mendelian disorders in a large Middle Eastern biobank
Aamer, W., Al-Maraghi, A., Syed, N., Gandhi, G. D., ALIYEV, E. E., Al-Kurbi, A. A., Al-Saei, O., Kohailan, M., Krishnamoorthy, N., Palaniswamy, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25560900
Apolipoprotein C3 drives adverse cardiac remodeling in ischemic heart failure
Han, Y., Zhao, Y., Zhou, Z., Liu, C., Chen, J., Miao, G., Zhang, L., Wang, Y., Li, J., Huang, W., et al. (2026) · BMC Medicine · doi:10.1186/s12916-026-04855-3
- Authors
- Huff, M. W., & Hegele, R. A.
- Affiliations
- Western University (CA)
- Venue
- Circulation Research
- Published
- 2013-05-24
- Volume
- 112
- Issue
- 11
- Pages
- 1405-1408
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2117124644
- Cited by
- 70
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 5 · 2013: 1
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Genome Canada
- Ontario Genomics
- Ontario Genomics Institute
- Canadian Institutes of Health Research (79853_1, 79523_1, 126045_1, 119350_1, MOP13430)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein C-III, lipoprotein metabolism, vascular biology, plasma triglycerides, chromosome 11q23, genetic association
- MeSH terms
- Animals, Humans, Triglycerides, Hypertriglyceridemia, Genetic Therapy, Oligonucleotides, Antisense, Apolipoprotein C-III
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