Angiopoietin-like protein 3 inhibitors and their effects on hyperlipidemia and atherosclerotic risk

Authors

  • Wanee Plengpanich Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Keywords:

ANGPTL3, inhibitor and atherosclerosis

Abstract

Angiopoietin-like protein 3 (ANGPTL3) has emerged as an important regulator of lipid metabolism. Current innovative therapeutic options using monoclonal antibodies, antisense oligonucleotide or vaccine approaches to block this protein may reduce the atherosclerosis risk in individuals with dyslipidemia. This review aimed to discuss the effectiveness of these new ANGPTL3 inhibitors. Currently, evinacumab and vupanorsen are effective ANGPTL3 inhibitors. These drugs are used to treat patients with hyperlipidemia. Moreover, both drugs were associated with a significant reduction in triglyceride and low density lipoprotein levels and may prevent the development of atherosclerosis.

Downloads

Download data is not yet available.

References

Wadström BN, Wulff AB, Pedersen KM, Jensen GB, Nordestgaard BG. Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischaemic stroke: a cohortbased study. Eur Heart J 2022;43:3258-69.

https://doi.org/10.1093/eurheartj/ehab705

Kiss L, Fûr G, Pisipati S, Rajalingamgari P, Ewald N, Singh V, et al. Mechanisms linking hypertriglyceridemia to acute pancreatitis. Acta Physiol (Oxf) 2023;237:e13916.

https://doi.org/10.1111/apha.13916

Quispe R, Sweeney T, Varma B, Agarwala A, Michos ED. Recent updates in hypertriglyceridemia management for cardiovascular disease prevention. Curr Atheroscler Rep 2022;24:767-78.

https://doi.org/10.1007/s11883-022-01052-4

Azarpazhooh MR, Najafi F, Darbandi M, Kiarasi S, Oduyemi T, Spence JD. Triglyceride/high-density lipoprotein cholesterol Ratio: a clue to metabolic syndrome, Insulin Resistance, and Severe Atherosclerosis. Lipids 2021;56:405-12.

https://doi.org/10.1002/lipd.12302

Biterova E, Esmaeeli M, Alanen HI, Saaranen M, Ruddock LW. Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease. Sci Rep 2018;8:6752.

https://doi.org/10.1038/s41598-018-25237-7

Camenisch G, Pisabarro MT, Sherman D, Kowalski J, Nagel M, Hass P, et al. ANGPTL3 stimulates endothelial cell adhesion and migration via integrin alpha vbeta 3 and induces blood vessel formation in vivo. J Biol Chem 2002;277:17281-90.

https://doi.org/10.1074/jbc.M109768200

Ono M, Shimizugawa T, Shimamura M, Yoshida K, NojiSakikawa C, Ando Y, et al. Protein region important for regulation of lipid metabolism in angiopoietin-like 3 (ANGPTL3): ANGPTL3 is cleaved and activated in vivo. J Biol Chem 2003;278:41804-9.

https://doi.org/10.1074/jbc.M302861200

Hassan M. ANGPLT3: A novel modulator of lipid metabolism. Glob Cardiol Sci Pract. 2017;2017:e201706.

https://doi.org/10.21542/gcsp.2017.6

Tikkanen E, Minicocci I, Hällfors J, Di Costanzo A, D'Erasmo L, Poggiogalle E, et al. Metabolomic signature of angiopoietin-like protein 3 deficiency in fasting and postprandial state. Arterioscler Thromb Vasc Biol 2019;39:665-74.

https://doi.org/10.1161/ATVBAHA.118.312021

Ahmad Z, Banerjee P, Hamon S, Chan KC, Bouzelmat A, Sasiela WJ, et al. Inhibition of angiopoietin-like protein 3 with a monoclonal antibody reduces triglycerides in Hypertriglyceridemia. Circulation 2019;140:470-86.

https://doi.org/10.1161/CIRCULATIONAHA.118.039107

Adam RC, Mintah IJ, Alexa-Braun CA, Shihanian LM, Lee JS, Banerjee P, et al. Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance. J Lipid Res 2020;61: 1271-86.

https://doi.org/10.1194/jlr.RA120000888

Rosenson RS, Gaudet D, Ballantyne CM, Baum SJ, Bergeron J, Kershaw EE, et al. Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial. Nat Med 2023;29:729-37.

https://doi.org/10.1038/s41591-023-02222-w

Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, et al. Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med 2020;383:711-20.

https://doi.org/10.1056/NEJMoa2004215

Stefanutti C, Chan DC, Di Giacomo S, Morozzi C, Watts GF. Long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia: real-world clinical experience. Pharmaceuticals (Basel) 2022;15.

https://doi.org/10.3390/ph15111389

Fachin A, De Carlo C, Maestro A, Zanon D, Barbi E, Maximova N. Rapid Resolution of life-threatening hypertriglyceridemia after evinacumab administration in a pediatric hsct recipient: a case report. Pharmaceuticals (Basel) 2023;16.

https://doi.org/10.20944/preprints202307.0658.v1

Shamsudeen I, McCrindle BW, Hegele RA. Treatment of homozygous familial hypercholesterolemia with ANGPTL3 Inhibitor, evinacumab. JCEM Case Rep. 2023;1:luad058.

https://doi.org/10.1210/jcemcr/luad058

Wiegman A, Greber-Platzer S, Ali S, Reijman MD, Brinton EA, Charng MJ, et al. Evinacumab for pediatric patients with homozygous familial hypercholesterolemia. Circulation 2023;149:343-53.

https://doi.org/10.1161/CIRCULATIONAHA.123.065529

Harada-Shiba M, Ali S, Gipe DA, Gasparino E, Son V, Zhang Y, et al. A randomized study investigating the safety, tolerability, and pharmacokinetics of evinacumab, an ANGPTL3 inhibitor, in healthy Japanese and Caucasian subjects. Atherosclerosis. 2020;314:33-40.

https://doi.org/10.1016/j.atherosclerosis.2020.10.013

Gaudet D, Karwatowska-Prokopczuk E, Baum SJ, Hurh E, Kingsbury J, Bartlett VJ, et al. Vupanorsen, an Nacetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia. Eur Heart J 2020;41: 3936-45.

https://doi.org/10.1093/eurheartj/ehaa689

Bergmark BA, Marston NA, Bramson CR, Curto M, Ramos V, Jevne A, et al. Effect of vupanorsen on nonhigh-density lipoprotein cholesterol levels in statintreated patients with elevated cholesterol: TRANSLATE-TIMI 70. Circulation 2022;145:1377-86.

https://doi.org/10.1161/CIRCULATIONAHA.122.059266

Foss-Freitas MC, Akinci B, Neidert A, Bartlett VJ, Hurh E, Karwatowska-Prokopczuk E, et al. Selective targeting of angiopoietin-like 3 (ANGPTL3) with vupanorsen for the treatment of patients with familial partial lipodystrophy (FPLD): results of a proof-of-concept study. Lipids Health Dis 2021;20:174.

https://doi.org/10.1186/s12944-021-01589-4

Fowler A, Sampson M, Remaley AT, Chackerian B. A VLP-based vaccine targeting ANGPTL3 lowers plasma triglycerides in mice. Vaccine 2021;39:5780-6.

https://doi.org/10.1016/j.vaccine.2021.08.077

Fukami H, Morinaga J, Nakagami H, Hayashi H, Okadome Y, Matsunaga E, et al. Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia. Cell Rep Med 2021; 2:100446.

https://doi.org/10.1016/j.xcrm.2021.100446

Downloads

Published

2024-04-01

How to Cite

1.
Plengpanich W. Angiopoietin-like protein 3 inhibitors and their effects on hyperlipidemia and atherosclerotic risk. Chula Med J [Internet]. 2024 Apr. 1 [cited 2024 Dec. 22];68(2). Available from: https://he05.tci-thaijo.org/index.php/CMJ/article/view/1479