Understanding the ins and outs of lipoprotein (a) metabolism
- PMID: 35695615
- DOI: 10.1097/MOL.0000000000000823
Understanding the ins and outs of lipoprotein (a) metabolism
Abstract
Purpose of review: This review summarizes our current understanding of the processes of apolipoprotein(a) secretion, assembly of the Lp(a) particle and removal of Lp(a) from the circulation. We also identify existing knowledge gaps that need to be addressed in future studies.
Recent findings: The Lp(a) particle is assembled in two steps: a noncovalent, lysine-dependent interaction of apo(a) with apoB-100 inside hepatocytes, followed by extracellular covalent association between these two molecules to form circulating apo(a).The production rate of Lp(a) is primarily responsible for the observed inverse correlation between apo(a) isoform size and Lp(a) levels, with a contribution of catabolism restricted to larger Lp(a) isoforms.Factors that affect apoB-100 secretion from hepatocytes also affect apo(a) secretion.The identification of key hepatic receptors involved in Lp(a) clearance in vivo remains unclear, with a role for the LDL receptor seemingly restricted to conditions wherein LDL concentrations are low, Lp(a) is highly elevated and LDL receptor number is maximally upregulated.
Summary: The key role for production rate of Lp(a) [including secretion and assembly of the Lp(a) particle] rather than its catabolic rate suggests that the most fruitful therapies for Lp(a) reduction should focus on approaches that inhibit production of the particle rather than its removal from circulation.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Similar articles
-
Sortilin enhances secretion of apolipoprotein(a) through effects on apolipoprotein B secretion and promotes uptake of lipoprotein(a).J Lipid Res. 2022 Jun;63(6):100216. doi: 10.1016/j.jlr.2022.100216. Epub 2022 Apr 22. J Lipid Res. 2022. PMID: 35469919 Free PMC article.
-
Apo(a) and ApoB Interact Noncovalently Within Hepatocytes: Implications for Regulation of Lp(a) Levels by Modulation of ApoB Secretion.Arterioscler Thromb Vasc Biol. 2022 Mar;42(3):289-304. doi: 10.1161/ATVBAHA.121.317335. Epub 2022 Jan 20. Arterioscler Thromb Vasc Biol. 2022. PMID: 35045727
-
Lipoprotein(a) catabolism: a case of multiple receptors.Pathology. 2019 Feb;51(2):155-164. doi: 10.1016/j.pathol.2018.11.003. Epub 2018 Dec 27. Pathology. 2019. PMID: 30595508 Review.
-
Lipoprotein(a) metabolism: potential sites for therapeutic targets.Metabolism. 2013 Apr;62(4):479-91. doi: 10.1016/j.metabol.2012.07.024. Epub 2012 Oct 4. Metabolism. 2013. PMID: 23040268 Free PMC article. Review.
-
The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate.J Clin Invest. 1994 Jun;93(6):2758-63. doi: 10.1172/JCI117292. J Clin Invest. 1994. PMID: 8201014 Free PMC article.
Cited by
-
Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling.Clin Proteomics. 2024 Mar 1;21(1):19. doi: 10.1186/s12014-024-09465-w. Clin Proteomics. 2024. PMID: 38429638 Free PMC article. Review.
-
Lipoprotein(a) in Familial Hypercholesterolemia.CJC Open. 2023 Sep 30;6(1):40-46. doi: 10.1016/j.cjco.2023.09.018. eCollection 2024 Jan. CJC Open. 2023. PMID: 38313344 Free PMC article.
-
LDL binding to cell receptors and extracellular matrix is proatherogenic in obesity but improves after bariatric surgery.J Lipid Res. 2023 Nov;64(11):100451. doi: 10.1016/j.jlr.2023.100451. Epub 2023 Sep 28. J Lipid Res. 2023. PMID: 37777014 Free PMC article.
-
Sex-Specific Differences in Lipoprotein Production and Clearance.Arterioscler Thromb Vasc Biol. 2023 Sep;43(9):1617-1625. doi: 10.1161/ATVBAHA.122.318247. Epub 2023 Jul 6. Arterioscler Thromb Vasc Biol. 2023. PMID: 37409532 Review.
-
Evidence and Uncertainties on Lipoprotein(a) as a Marker of Cardiovascular Health Risk in Children and Adolescents.Biomedicines. 2023 Jun 8;11(6):1661. doi: 10.3390/biomedicines11061661. Biomedicines. 2023. PMID: 37371756 Free PMC article. Review.
References
-
- Patel AP, Wang M, Pirruccello JP, et al. Lp(a) (Lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease: new insights from a large national Biobank. Arterioscler Thromb Vasc Biol 2021; 41:465–474.
-
- Rader DJ, Cain W, Ikewaki K, et al. The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. J Clin Invest 1994; 93:2758–2763.
-
- Wang J, White AL. Role of N-linked glycans, chaperone interactions and proteasomes in the intracellular targeting of apolipoprotein(a). Biochem Soc Trans 1999; 27:453–458.
-
- White AL, Guerra B, Wang J, Lanford RE. Presecretory degradation of apolipoprotein [a] is mediated by the proteasome pathway. J Lipid Res 1999; 40:275–286.
-
- White AL, Guerra B, Lanford RE. Influence of allelic variation on apolipoprotein(a) folding in the endoplasmic reticulum. J Biol Chem 1997; 272:5048–5055.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous