Commentary (original) (raw)
Journal Article
National Institutes of Health
, Bethesda, MD
Address correspondence to the author at: National Institutes of Health, Bldg. 10, Rm. 2C-433, 10 Center Dr, MSC 1508, Bethesda, MD, 20892-1508. Fax 301-402-1885; e-mail aremaley@nih.gov.
Search for other works by this author on:
Navbar Search Filter Mobile Enter search term Search
Although apolipoprotein (apo)A-I and apoB are measured by many laboratories as an adjunct to HDL and LDL concentrations, respectively, lipoproteins contain numerous other proteins, some of which have a profound effect on lipoprotein metabolism. ApoE, for example, resides on both antiatherogenic HDL particles and on proatherogenic apoB-containing lipoproteins, thus confounding the usefulness of apoE as a cardiovascular risk marker in unfractionated samples. Nevertheless, apoE has many different roles in lipoprotein metabolism, some of which may account for the macrophage lipid accumulation observed in this interesting case. The best understood function of apoE is that it can serve as a ligand for the cellular uptake of apoB-containing proteins, as well as perhaps HDL, by various receptors. In the absence of a normal form of apoE, there is decreased hepatic clearance of lipoproteins, which leads to their increased oxidation and uptake by macrophage scavenger receptors. ApoE can also help prevent lipid accumulation in cells, particularly in macrophages, which synthesize apoE, by promoting the efflux of excess intracellular cholesterol by the ABCA1 transporter and by other cholesterol efflux mechanisms.
Recently, a new role for apoE has been described, which may also be relevant to the macrophage lipid accumulation observed in this case. The presence of apoE on lipoproteins also facilitates the lysosomal processing of endocytosed lipoproteins (1). In the absence of apoE or possibly, as in this case, in the presence of an abnormal form of apoE, the endocytosed lipoproteins interfere with the delivery of the various hydrolytic enzymes to the lysosome, by perhaps altering the production and/or trafficking of the mannose-6-phosphate receptor, which normally shepherds these enzymes to the lysosome. This interference results in a defect in the intracellular lipolysis of lipoproteins and the accumulation of cholesteryl esters in lysososomes. In addition, cathepsin B, normally a lysosomal proteolytic enzyme, is instead secreted into the extracellular space, where it may contribute to the formation of unstable plaques. Currently, the only apoE-based test routinely performed in clinical laboratories is a genotype type test for apoE isoforms, for assessing the risk of Alzheimer disease. Given the multifaceted role of apoE in lipoprotein metabolism, the measurement of apoE on specific lipoprotein fractions may be a fruitful area for future research on cardiovascular risk markers.
Grant/funding Support: None declared.
Financial Disclosures: None declared.
References
1
Wu D, Sharan C, Yang H, Goodwin JS, Zhou L, Grabowski GA, Du H, Guo Z. Apolipoprotein E-deficient lipoproteins induce foam cell formation by downregulation of lysosomal hydrolases in macrophages.
J Lipid Res
2007
;
48
:
2571
-2578.
© 2008 The American Association for Clinical Chemistry
Citations
Views
Altmetric
Metrics
Total Views 787
96 Pageviews
691 PDF Downloads
Since 1/1/2020
Month: | Total Views: |
---|---|
January 2020 | 2 |
February 2020 | 2 |
April 2020 | 3 |
May 2020 | 2 |
June 2020 | 1 |
July 2020 | 7 |
August 2020 | 9 |
September 2020 | 34 |
October 2020 | 38 |
November 2020 | 33 |
December 2020 | 35 |
January 2021 | 31 |
February 2021 | 30 |
March 2021 | 27 |
April 2021 | 42 |
May 2021 | 16 |
June 2021 | 14 |
July 2021 | 22 |
August 2021 | 20 |
September 2021 | 47 |
October 2021 | 32 |
November 2021 | 29 |
December 2021 | 23 |
January 2022 | 37 |
February 2022 | 9 |
March 2022 | 16 |
April 2022 | 24 |
May 2022 | 24 |
June 2022 | 26 |
July 2022 | 26 |
August 2022 | 18 |
September 2022 | 22 |
October 2022 | 19 |
November 2022 | 8 |
December 2022 | 3 |
January 2023 | 3 |
February 2023 | 1 |
March 2023 | 3 |
April 2023 | 2 |
May 2023 | 6 |
August 2023 | 2 |
September 2023 | 3 |
October 2023 | 3 |
November 2023 | 6 |
December 2023 | 6 |
February 2024 | 4 |
March 2024 | 3 |
April 2024 | 3 |
May 2024 | 2 |
June 2024 | 2 |
July 2024 | 2 |
September 2024 | 5 |
×
Email alerts
Citing articles via
More from Oxford Academic