Current and Emerging Reconstituted HDL-apoA-I and HDL-apoE Approaches to Treat Atherosclerosis
- PMID: 30282955
- PMCID: PMC6313318
- DOI: 10.3390/jpm8040034
Current and Emerging Reconstituted HDL-apoA-I and HDL-apoE Approaches to Treat Atherosclerosis
Abstract
Atherosclerosis affects millions of people worldwide. However, the wide variety of limitations in the current therapeutic options leaves much to be desired in future lipid-lowering therapies. For example, although statins, which are the first-line treatment for coronary heart disease (CHD), reduce the risk of cardiovascular events in a large percentage of patients, they lead to optimal levels of low density lipoprotein-cholesterol (LDL-C) in only about one-third of patients. A new promising research direction against atherosclerosis aims to improve lipoprotein metabolism. Novel therapeutic approaches are being developed to increase the levels of functional high density lipoprotein (HDL) particles. This review aims to highlight the atheroprotective potential of the in vitro synthesized reconstituted HDL particles containing apolipoprotein E (apoE) as their sole apolipoprotein component (rHDL-apoE). For this purpose, we provide: (1) a summary of the atheroprotective properties of native plasma HDL and its apolipoprotein components, apolipoprotein A-I (apoA-I) and apoE; (2) an overview of the anti-atherogenic functions of rHDL-apoA-I and apoA-I-containing HDL, i.e., natural HDL isolated from transgenic Apoa1-/- × Apoe-/- mice overexpressing human apoA-I (HDL-apoA-I); and (3) the latest developments and therapeutic potential of HDL-apoE and rHDL-apoE. Novel rHDL formulations containing apoE could possibly present enhanced biological functions, leading to improved therapeutic efficacy against atherosclerosis.
Keywords: apolipoprotein A-I; apolipoprotein E; atherosclerosis; lipoprotein metabolism; reconstituted HDL.
Conflict of interest statement
The authors declare no conflict of interest.
Similar articles
-
Structure-function relationships in reconstituted HDL: Focus on antioxidative activity and cholesterol efflux capacity.Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Sep;1862(9):890-900. doi: 10.1016/j.bbalip.2017.05.010. Epub 2017 May 18. Biochim Biophys Acta Mol Cell Biol Lipids. 2017. PMID: 28529180
-
ApoE induces serum paraoxonase PON1 activity and stability similar to ApoA-I.Biochemistry. 2010 Jan 26;49(3):532-8. doi: 10.1021/bi9013227. Biochemistry. 2010. PMID: 20025294
-
HDL-apoA-I induces the expression of angiopoietin like 4 (ANGPTL4) in endothelial cells via a PI3K/AKT/FOXO1 signaling pathway.Metabolism. 2018 Oct;87:36-47. doi: 10.1016/j.metabol.2018.06.002. Epub 2018 Jun 18. Metabolism. 2018. PMID: 29928895
-
Therapeutic applications of reconstituted HDL: When structure meets function.Pharmacol Ther. 2016 Jan;157:28-42. doi: 10.1016/j.pharmthera.2015.10.010. Epub 2015 Nov 10. Pharmacol Ther. 2016. PMID: 26546991 Review.
-
Pitavastatin: novel effects on lipid parameters.Atheroscler Suppl. 2011 Nov;12(3):277-84. doi: 10.1016/S1567-5688(11)70887-X. Atheroscler Suppl. 2011. PMID: 22152282 Review.
Cited by
-
Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies.Pharmaceuticals (Basel). 2022 Oct 18;15(10):1278. doi: 10.3390/ph15101278. Pharmaceuticals (Basel). 2022. PMID: 36297390 Free PMC article. Review.
-
The Mechanism of Bisphenol A Atherogenicity Involves Apolipoprotein A-I Downregulation through NF-κB Activation.Int J Mol Sci. 2019 Dec 12;20(24):6281. doi: 10.3390/ijms20246281. Int J Mol Sci. 2019. PMID: 31842455 Free PMC article.
-
Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties.Arterioscler Thromb Vasc Biol. 2024 Jun;44(6):1191-1201. doi: 10.1161/ATVBAHA.124.320851. Epub 2024 Apr 25. Arterioscler Thromb Vasc Biol. 2024. PMID: 38660807 Free PMC article. Review.
-
HDL in Immune-Inflammatory Responses: Implications beyond Cardiovascular Diseases.Cells. 2021 Apr 29;10(5):1061. doi: 10.3390/cells10051061. Cells. 2021. PMID: 33947039 Free PMC article. Review.
-
High Density Lipoprotein and Its Precursor Protein Apolipoprotein A1 as Potential Therapeutics to Prevent Anthracycline Associated Cardiotoxicity.Front Cardiovasc Med. 2020 Apr 28;7:65. doi: 10.3389/fcvm.2020.00065. eCollection 2020. Front Cardiovasc Med. 2020. PMID: 32411725 Free PMC article. Review.
References
-
- Mozaffarian D., Benjamin E.J., Go A.S., Arnett D.K., Blaha M.J., Cushman M., de Ferranti S., Després J.-P., Fullerton H.J., Howard V.J., et al. Heart disease and stroke statistics—2015 update: A report from the American Heart Association. Circulation. 2015;131:e29–e322. doi: 10.1161/CIR.0000000000000152. - DOI - PubMed
-
- Mozaffarian D., Benjamin E.J., Go A.S., Arnett D.K., Blaha M.J., Cushman M., Das S.R., de Ferranti S., Després J.-P., Fullerton H.J., et al. Stroke Statistics Subcommittee executive summary: Heart disease and stroke statistics—2016 Update: A report from the American Heart Association. Circulation. 2016;133:447–454. doi: 10.1161/CIR.0000000000000366. - DOI - PubMed
-
- Harrison D.G. Endothelial dysfunction in atherosclerosis. Basic Res. Cardiol. 1994;89:87–102. - PubMed
Publication types
Grants and funding
- MIS 5002802/The grand "The Greek Research Infrastructure for Personalised Medicine" is funded by the Operational Programme "Competitiveness, Entrepreneurship and Innovation" and co-financed by Greece and the European Union (European Regional Development Fund)
- MIS 5006782/The grant "In vitro and in vivo evaluation of the atheroprotective role of reconstituted HDL containing apolipoprotein E3" is co-financed by Greece and the European Union (European Social Fund) by the "Human Resources Development, Education and Lifelong L
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous