Angiopoietin-Like Protein3 Regulates Plasma HDL Cholesterol Through Suppression of Endothelial Lipase
Abstract
Objectives— A low level of high-density lipoprotein (HDL) in plasma has been recognized as an aspect of metabolic syndrome and as a crucial risk factor of cardiovascular events. However, the physiological regulation of plasma HDL levels has not been completely defined. Current studies aim to reveal the contribution of angiopoietin-like protein3 (angptl3), previously known as a plasma suppressor of lipoprotein lipase, to HDL metabolism. Methods and Results— Angptl3-deficient mice showed low plasma HDL cholesterol and HDL phospholipid (PL), and which were increased by ANGPTL3 supplementation via adenovirus. In vitro, ANGPTL3 inhibited the phospholipase activity of endothelial lipase (EL), which hydrolyzes HDL-PL and hence decreases plasma HDL levels, through a putative heparin-binding site in the N-terminal domain of ANGPTL3. Post-heparin plasma in Angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous EL is elevated in Angptl3-deficient mice. Furthermore, we established an ELISA system for human ANGPTL3 and found that plasma ANGPTL3 levels significantly correlated with plasma HDL cholesterol and HDL-PL levels in human subjects. Conclusions— Angptl3 acts as an inhibitor of EL and may be involved in the regulation of plasma HDL cholesterol and HDL-PL levels in humans and rodents.
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ANGPTL3 inhibits lipoprotein lipase, which results in increased blood lipid levels.
“ANGPTL3 inhibits the lipoprotein lipase, which results in increased blood lipid levels [143–145].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [145]
Evinacumab is a monoclonal antibody inhibiting angiopoietin-like 3 (ANGPTL3).
“Evinacumab is a monoclonal antibody inhibiting angiopoietin-like 3 (ANGPTL3).”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [145]
The paper’s ‘ANGPTL3 Inhibited EL Activity In Vitro’ section examines ANGPTL3’s effects on endothelial lipase, not a drug that inhibits ANGPTL3. A search for evinacumab and ANGPTL3-inhibiting antibodies found no passage identifying evinacumab or describing it as a monoclonal antibody; the antibody in ‘Western Blotting’ is used for an assay. (LLM, conf=0.76)
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- Authors
- Shimamura, M., Matsuda, M., Yasumo, H., Okazaki, M., Fujimoto, K., Kono, K., Shimizugawa, T., Ando, Y., Koishi, R., Kohama, T., Sakai, N., Kotani, K., Komuro, R., Ishida, T., Hirata, K., Yamashita, S., Furukawa, H., & Shimomura, I.
- Affiliations
- Tokyo Medical and Dental University (JP)
- From the Department of Medicine and Pathophysiology (M.S., M.M., I.S.), Graduate School of Frontier Bioscience; Department of Metabolic Medicine (M.M., N.S., R.Komuro, I.S.), Department of Cardiovascular Medicine (S.Y.), Graduate School of Medicine, Osaka University, Osaka, Japan; Biomedical Research Laboratories (M.S., H.Y., R.Koishi, T.K., H.F.), Pharmacology and Molecular Biology Research Laboratories (K.Kono, T.S., T.K.), Sankyo Co. Ltd., Tokyo, Japan; Medical Safety Research Laboratories (K.F.,...
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2007-02
- Volume
- 27
- Issue
- 2
- Pages
- 366-372
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W1986046837
- Semantic Scholar
- 11e4481b3e3eddf07edd0140b171265c76098990
- Cited by
- 297
- References
- 23
- Citations by year
- 2026: 10 · 2025: 24 · 2024: 17 · 2023: 20 · 2022: 20 · 2021: 38 · 2020: 15 · 2019: 15 · 2018: 16 · 2017: 13 · 2016: 12 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 19
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- ANGPTL3, endothelial lipase, HDL cholesterol, HDL phospholipids, lipoprotein metabolism, heparin-binding site, lipoprotein lipase, metabolic syndrome, cardiovascular risk, serum lipoproteins
- MeSH terms
- Angiopoietin-like Proteins, Angiopoietin-Like Protein 3, Animals, Humans, Lipase, Cholesterol, HDL, Male, Recombinant Proteins, Gene Expression Regulation, Enzymologic, Mice, Knockout, Intercellular Signaling Peptides and Proteins, Angiopoietins, Mice
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