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Cited by 47Lipid metabolism and disordersLipoproteins and Cardiovascular HealthCholesterol and Lipid Metabolism

Unlocking the mysteries of VLDL: exploring its production, intracellular trafficking, and metabolism as therapeutic targets

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Chen, Jingfei, Fang, Zhenfei, Luo, Qin, Wang, Xiao, Warda, Mohamad, Das, Avash, Oldoni, Federico, Luo, Fei·2024·Lipids in Health and Disease
DOI 10.1186/s12944-023-01993-yPMC PMC10785355
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Abstract

Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD.

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  • ANGPTL3 inhibition accelerates triglyceride-rich lipoprotein processing and reduces LDL precursors while enhancing HDL catabolism.

    “In contrast, ANGPTL3 inhibition accelerates triglyceride-rich lipoprotein processing and reduces LDL precursors while enhancing HDL catabolism, accounting for concurrent LDL-C reduction and modest HDL-C decrease (Zhang, 2021; Chen et al., 2024; Adam et al., 2020; Wang et al., 2015; Yasuda et al., 2010; Hooper and Burnett, 2013).”

    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 Chen et al., 2024

    The ‘Targeting ANGPTL3’ section (page unavailable) says ANGPTL3 inhibition promotes VLDL-remnant clearance, hastens VLDL processing before LDL production, and reduces LDL-C. It identifies ANGPTL3 as an endothelial-lipase inhibitor, but does not state that its inhibition enhances HDL catabolism or causes a modest HDL-C decrease. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Chen, J., Fang, Z., Luo, Q., Wang, X., Warda, M., Das, A., Oldoni, F., & Luo, F.
Affiliations
  • Central South University (CN)
  • Peking University (CN)
  • Cairo University (EG)
  • Beth Israel Deaconess Medical Center (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Luo, Fei
ORCID
Venue
Lipids in Health and Disease
Publisher
Springer Science and Business Media LLC
Published
2024-01-12
Volume
23
Issue
1
Pages
14-14
ISSN
1476-511X (ISSN-L)
DOI
10.1186/s12944-023-01993-y
PMC
PMC10785355
OpenAlex
W4390789318
Cited by
47
References
15
Citations by year
2026: 17 · 2025: 21 · 2024: 9
FWCI
14.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Lipids in Health and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Ataturk University - AVESIS (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Greater South Information System
Funders
  • National Natural Science Foundation of China (82201879, 82100495)
  • Hunan Provincial Natural Science Foundation of China (2022JJ40675, 2021JJ40852)
  • Scientific Research Project of Hunan Provincial Health Commission (202305037231, 202203014009)
  • Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University
  • China Postdoctoral Science Foundation
  • Key Research and Development Program of Hunan Province of China (2021SK2004)
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
VLDL, VLDL production, VLDL metabolism, intracellular trafficking, lipid modification, lipid secretion, atherosclerotic cardiovascular disease, residual cardiovascular risk, mipomersen, lomitapide, ANGPTL3 inhibitors, triglycerides, serum cholesterol
MeSH terms
Angiopoietin-Like Protein 3, Cholesterol, Humans, Lipoproteins, LDL, Lipoproteins, VLDL, Receptors, LDL, Atherosclerosis

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