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Cited by 7Lipid metabolism and disordersLipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and Lipoproteins

Managing of dyslipidaemia characterized by accumulation of triglyceride-rich lipoproteins

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Visser, Jolien, van Zwol, Willemien, Kuivenhoven, Jan Albert·2022·Current Atherosclerosis Reports
DOI 10.1007/s11883-022-00979-yPMC PMC8924084
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Abstract

Purpose of Review: The accumulation of triglyceride-rich lipoproteins (TRLs) in plasma in patients with familial chylomicronaemia syndrome (FCS) or severe hypertriglyceridemia is associated with an increased risk of potentially life-threatening pancreatitis. Elevated TRL levels have also been suggested to contribute to atherosclerotic cardiovascular disease (ASCVD). This review provides the latest progress that has been made in this field of research. Recent Findings: Apolipoprotein C-III and angiopoietin-like protein 3 play key roles in the metabolism of TRLs. Targeting their production in the liver or their presence in the circulation effectively reduces triglycerides in patients with FCS or severe hypertriglyceridemia. Attempts to reduce triglyceride synthesis in the small intestine have been halted. Early studies with a fibroblast growth factor 21 agonist have shown to reduce plasma triglycerides and hepatic steatosis and improve glucose homeostasis. Summary: New drugs have recently been shown to effectively reduce plasma triglycerides which render hope for treating the risk of pancreatitis. Studies that have just been initiated will learn whether this unmet clinical will be met. It is too early to evaluate the potential of these drugs to reduce the risk of atherosclerosis through the reduction of triglycerides.

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  • APOC3 inhibition primarily enhances peripheral clearance of triglyceride-rich lipoproteins without substantially affecting hepatic VLDL production or LDL metabolism.

    “APOC3 inhibition primarily enhances peripheral clearance of triglyceride-rich lipoproteins without substantially affecting hepatic VLDL production or LDL metabolism, explaining neutral LDL-C effects and a tendency toward higher HDL-C levels (Malick et al., 2023b; Zhang, 2021; Visser et al., 2022; Khetarpal et al., 2017; Chen et al., 2024).”

    From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Visser et al., 2022

    The APOC3 Antagonists section (page unavailable) says apoC-III is thought to inhibit lipoprotein lipase-mediated triglyceride lipolysis, supporting a role for APOC3 inhibition in clearing triglyceride-rich lipoproteins. It also says apoC-III interferes with hepatic clearance, so the source does not establish that the effect is primarily peripheral. The section does not establish negligible effects on VLDL production or LDL metabolism, or the proposed explanation for LDL-C and HDL-C changes. (LLM, conf=0.84)

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Research works printed but not linked: 30

  1. [1]Laufs U Parhofer KG Ginsberg HN Hegele RA Clinical review on triglycerides Eur Heart J 2020 41 99 109c 10.1093/eurheartj/ehz785 31764986 PMC6938588 · DOI · Paper page
  2. [2]Holmes MV Asselbergs FW Palmer TM Drenos F Lanktree MB Nelson CP Mendelian randomization of blood lipids for coronary heart disease Eur Heart J 2015 36 539 550 10.1093/eurheartj/eht571 24474739 PMC4344957 · DOI · Paper page
  3. [3]Allara E Morani G Carter P Gkatzionis A Zuber V Foley CN Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation Circ Genomic Precis Med 2019 12 e002711 10.1161/CIRCGEN.119.002711 PMC6922071 31756303 · DOI
  4. [4]Lee SH Lee JY Kim GH Jung KJ Lee S Kim HC Two-sample mendelian randomization study of lipid levels and ischemic heart disease Korean Circ J 2020 50 940 948 10.4070/kcj.2020.0131 32812402 PMC7515757 · DOI
  5. [5]Do R Willer CJ Schmidt EM Sengupta S Gao C Peloso GM Common variants associated with plasma triglycerides and risk for coronary artery disease Nat Genet 2013 45 1345 1352 10.1038/ng.2795 24097064 PMC3904346 · DOI · Paper page
  6. [7]Sun C Alkhoury K Wang YI Foster GA Radecke CE Tam K IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal Circ Res 2012 111 1054 1064 10.1161/CIRCRESAHA.112.270314 22874466 PMC3810165 · DOI
  7. [9]Varbo A Benn M Tybjærg-Hansen A Nordestgaard BG Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation Circulation 2013 128 1298 1309 10.1161/CIRCULATIONAHA.113.003008 23926208 · DOI · Paper page
  8. [12]Hegele RA Ginsberg HN Chapman MJ Nordestgaard BG Kuivenhoven JA Averna M The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management Lancet Diabetes Endocrinol 2014 2 655 666 10.1016/S2213-8587(13)70191-8 24731657 PMC4201123 · DOI · Paper page
  9. [14]Das S McCreary J Shamim S Kalayjian T Reversal of severe hypertriglyceridemia with intermittent fasting and a very-low-carbohydrate ketogenic diet: a case series Curr Opin Endocrinol Diabetes Obes 2020 27 308 311 10.1097/MED.0000000000000566 32740049 · DOI
  10. [18]Mäkinen P Ruotsalainen AK Ylä-Herttuala S Nucleic acid–based therapies for atherosclerosis Curr Atheroscler Rep 2020 22 10 10.1007/s11883-020-0826-2 32034521 PMC7007442 · DOI
  11. [21]Springer AD Dowdy SF GalNAc-siRNA Conjugates: leading the way for delivery of RNAi therapeutics Nucleic Acid Ther 2018 28 109 118 10.1089/nat.2018.0736 29792572 PMC5994659 · DOI · Paper page
  12. [22]Alexander VJ Xia S Hurh E Hughes SG O’Dea L Geary RS N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels Eur Heart J 2019 40 2785 2796 10.1093/eurheartj/ehz209 31329855 PMC6736334 · DOI · Paper page
  13. [28]Koishi R Ando Y Ono M Shimamura M Yasumo H Fujiwara T Angptl3 regulates lipid metabolism in mice Nat Genet 2002 30 151 157 10.1038/ng814 11788823 · DOI
  14. [29]Musunuru K Pirruccello JP Do R Peloso GM Guiducci C Sougnez C Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia N Engl J Med 2010 363 2220 2227 10.1056/NEJMoa1002926 20942659 PMC3008575 · DOI · Paper page
  15. [30]Xu YX Redon V Yu H Querbes W Pirruccello J Liebow A Role of angiopoietin-like 3 (ANGPTL3) in regulating plasma level of low-density lipoprotein cholesterol Atherosclerosis 2018 268 196 206 10.1016/j.atherosclerosis.2017.08.031 29183623 PMC5750127 · DOI
  16. [31]Adam RC Mintah IJ Alexa-Braun CA Shihanian LM Lee JS Banerjee P Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance J Lipid Res 2020 61 1271 1286 10.1194/jlr.RA120000888 32646941 PMC7469887 · DOI · Paper page
  17. [32]Ruscica M Zimetti F Adorni MP Sirtori CR Lupo MG Ferri N Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: new therapeutic approaches for the treatment of atherogenic dyslipidemia Pharmacol Res 2020 153 104653 10.1016/j.phrs.2020.104653 31931117 · DOI
  18. [33]Gaudet D Gipe DA Pordy R Ahmad Z Cuchel M Shah PK ANGPTL3 inhibition in homozygous familial hypercholesterolemia N Engl J Med 2017 377 222 232 10.1056/NEJMc1705994 28723334 · DOI · Paper page
  19. [34]Raal FJ Rosenson RS Reeskamp LF Hovingh GK Kastelein JJP Rubba P Evinacumab for homozygous familial hypercholesterolemia N Engl J Med. 2020 383 711 20 10.1056/NEJMoa2004215 32813947 · DOI · Paper page
  20. [35]•• Rosenson RS. A phase 2 trial of the efficacy and safety of evinacumab in patients with severe hypertriglyceridemia. Presented at ACC 2021. 2021 [cited 2021 May 16]. Available from: https://www.acc.org/about-acc/press-releases/2021/05/15/21/19/evinacumab-could-help-some-patients-with-severe-hypertriglyceridemia. Provides the latest data of Evinacumab in patients with severe hypertriglyceridemia.
  21. [37]Gaudet D Karwatowska-Prokopczuk E Baum SJ Hurh E Kingsbury J Bartlett VJ Vupanorsen, an N-acetyl 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 10.1093/eurheartj/ehaa689 32860031 PMC7750927 · DOI · Paper page
  22. [39]Sacks FM, Stanesa M, Hegele RA. Severe hypertriglyceridemia with pancreatitis: thirteen years’ treatment with lomitapide. JAMA Intern Med. 2014;174:443–7. 24366202
  23. [40]Senior M After Glybera’s withdrawal, what’s next for gene therapy? Nat Biotechnol 2017 35 491 492 10.1038/nbt0617-491 28591128 · DOI
  24. [41]Scott LJ Alipogene tiparvovec: a review of its use in adults with familial lipoprotein lipase deficiency Drugs 2015 75 175 182 10.1007/s40265-014-0339-9 25559420 · DOI
  25. [42]Jackson KG Poppitt SD Minihane AM Postprandial lipemia and cardiovascular disease risk: interrelationships between dietary, physiological and genetic determinants Atherosclerosis 2012 220 22 33 10.1016/j.atherosclerosis.2011.08.012 21955695 · DOI · Paper page
  26. [43]Blom DJ Raal FJ Santos RD Marais AD Lomitapide and mipomersen-inhibiting microsomal triglyceride transfer protein (MTP) and apoB100 synthesis Curr Atheroscler Rep 2019 21 48 10.1007/s11883-019-0809-3 31741187 · DOI
  27. [44]van Rijn JM Ardy RC Kuloğlu Z Härter B van Haaften-Visser DY van der Doef HPJ Intestinal failure and aberrant lipid metabolism in patients with DGAT1 deficiency Gastroenterology 2018 155 130 143 10.1053/j.gastro.2018.03.040 29604290 PMC6058035 · DOI
  28. [47]Zarei M Pizarro-Delgado J Barroso E Palomer X Vázquez-Carrera M Targeting FGF21 for the treatment of nonalcoholic steatohepatitis Trends Pharmacol Sci 2020 41 199 208 10.1016/j.tips.2019.12.005 31980251 · DOI
  29. [51]Nordestgaard BM Chapman JM Humphries SM Ginsberg HN Masana L Descamps OS Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European atherosclerosis society Eur Heart J 2013 34 3478 3490 10.1093/eurheartj/eht273 23956253 PMC3844152 · DOI · Paper page
  30. [52]Stoner KL Harder H Fallowfield LJ Jenkins VA Intravenous versus subcutaneous drug administration. Which do patients prefer? A systematic review Patient 2015 8 145 53 10.1007/s40271-014-0075-y 25015302 · DOI

Cited by

Sorted by citations

Authors
Visser, J., van Zwol, W., & Kuivenhoven, J. A.
Affiliations
University Medical Center Groningen (NL)
Corresponding author
Kuivenhoven, Jan Albert
ORCID
Kuivenhoven, Jan Albert
Venue
Current Atherosclerosis Reports
Publisher
Springer Science and Business Media LLC
Published
2022-01
Volume
24
Issue
1
Pages
1-12
ISSN
  • 1523-3804 (ISSN-L)
  • 1534-6242
DOI
10.1007/s11883-022-00979-y
PMC
PMC8924084
OpenAlex
W4210473424
Cited by
7
References
13
Citations by year
2026: 1 · 2025: 2 · 2023: 4
FWCI
0.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Atherosclerosis Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
hartstichting (2015T068, CVON2017-2020)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
dyslipidemia, triglyceride-rich lipoproteins, severe hypertriglyceridemia, pancreatitis, atherosclerotic cardiovascular disease, apolipoprotein C-III, ANGPTL3, FGF21, hepatic steatosis, glucose homeostasis, triglyceride-lowering drugs
MeSH terms
Humans, Lipoproteins, Pancreatitis, Triglycerides, Hypertriglyceridemia, Atherosclerosis, Apolipoprotein C-III

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