Lipoproteins within the lymphatic system: Insights into health, disease, and therapeutic implications

Malaz Yousef, Nadia Bou Chacra, Neal M. Davies, Raimar Löbenberg

Article ID: 2202
Vol 6, Issue 2, 2023

VIEWS - 832 (Abstract) 189 (PDF)

Abstract


This analysis of contemporary findings aims to enhance our understanding of lipoprotein biology within the lymphatic system and its relevance to human health and disease. It delves into the complex interrelationship between lipoproteins and the lymphatic system, encompassing their diverse classes and pivotal roles in the absorption and transport of drugs, vitamins, and xenobiotics. Lipoproteins consist of a hydrophobic core comprising non-polar lipids and a hydrophilic membrane composed of phospholipids, free cholesterol, and apolipoproteins. The lymphatic system collaborates with lipoproteins in the absorption and transport of dietary lipids. Simultaneously, it plays a vital role in the regulation of body fluid levels and acts as a formidable defense mechanism against infections. Lipoprotein classes encompass chylomicrons, chylomicron remnants, very low-density lipoproteins, intermediate density lipoproteins, low-density lipoproteins, high-density lipoproteins, and lipoprotein (a). Understanding the intricate relationship between lipoproteins and the lymphatic system holds immense implications for comprehending the underlying pathological processes of various diseases such as atherosclerosis, diabetes and obesity among others. By shedding light on the interplay between lipoproteins and the lymphatic system, this report underscores the significance of conducting research that contributes to the advancement of our knowledge in this field. Ultimately, such research paves the way for potential therapeutic interventions and novel strategies to address numerous disorders.


Keywords


lymphatic; lipoproteins; chylomicrons; drug delivery; pathophysiology

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References


1. Brouillette CG, Anantharamaiah GM, Engler JA, Borhani DW. Structural models of human apolipoprotein A-I: A critical analysis and review. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 2001; 1531(1–2): 4–46. doi: 10.1016/S1388-1981(01)00081-6

2. Afonso CB, Spickett CM. Lipoproteins as targets and markers of lipoxidation. Redox Biology 2019; 23: 101066. doi: 10.1016/j.redox.2018.101066

3. Morrisett JD, Jackson RL, Gotto AM. Lipoproteins: Structure and function. Annual Review of Biochemistry 1975; 44(1): 183–207. doi: 10.1146/annurev.bi.44.070175.001151

4. Feingold KR. Introduction to lipids and lipoproteins. Available online: https://www.ncbi.nlm.nih.gov/books/NBK305896/ (accessed on 30 August 2023).

5. Smith LC, Pownall HJ, Gotto AM. The plasma lipoproteins: Structure and metabolism. Annual Review of Biochemistry 1978; 47(1): 751–777. doi: 10.1146/annurev.bi.47.070178.003535

6. Yousef M, Silva D, Chacra NB, et al. The lymphatic system: A sometimes-forgotten compartment in pharmaceutical sciences. Journal of Pharmacy and Pharmaceutical Sciences 2021; 24: 533–547. doi: 10.18433/jpps32222

7. O’Brien PJ, Alborn WE, Sloan JH, et al. The novel apolipoprotein A5 is present in human serum, is associated with VLDL, HDL, and chylomicrons, and circulates at very low concentrations compared with other apolipoproteins. Clinical Chemistry 2005; 51(2): 351–359. doi: 10.1373/clinchem.2004.040824

8. Pirillo A, Catapano AL. Lipoprotein remnants: To be or not to be. European Heart Journal 2021; 42(47): 4844–4846. doi: 10.1093/eurheartj/ehab511

9. Chaudhary S, Garg T, Murthy RS, et al. Recent approaches of lipid-based delivery system for lymphatic targeting via oral route. Journal of Drug Targeting 2014; 22(10): 871–882. doi: 10.3109/1061186X.2014.950664

10. Masulli M, Patti L, Riccardi G, et al. Relation among lipoprotein subfractions and carotid atherosclerosis in Alaskan Eskimos (from the GOCADAN Study). The American Journal of Cardiology 2009; 104(11): 1516–1521. doi: 10.1016/j.amjcard.2009.07.021

11. Rigotti A. Absorption, transport, and tissue delivery of vitamin E. Molecular Aspects of Medicine 2007; 28(5–6): 423–436. doi: 10.1016/j.mam.2007.01.002

12. Liu X, Suo R, Xiong SL, et al. HDL drug carriers for targeted therapy. Clinica Chimica Acta 2013; 415: 94–100. doi: 10.1016/j.cca.2012.10.008

13. Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nature Reviews Molecular Cell Biology 2008; 9(2): 125–138. doi: 10.1038/nrm2336

14. Bell FP. The effect of fat-soluble xenobiotics on intestinal lipid, apoprotein, and lipoprotein synthesis and secretion. In: Fat Absorption, 1st ed. CRC Press; 2018. pp. 167–188.

15. Dahan A, Hoffman A. Evaluation of a chylomicron flow blocking approach to investigate the intestinal lymphatic transport of lipophilic drugs. European Journal of Pharmaceutical Sciences 2005; 24(4): 381–388. doi: 10.1016/j.ejps.2004.12.006

16. Hokkanen K, Tirronen A, Ylä-Herttuala S. Intestinal lymphatic vessels and their role in chylomicron absorption and lipid homeostasis. Current Opinion in Lipidolog 2019; 30(5): 370–376. doi: 10.1097/MOL.0000000000000626

17. Cifarelli V, Eichmann A. The intestinal lymphatic system: Functions and metabolic implications. Cellular and Molecular Gastroenterology and Hepatology 2019; 7(3): 503–513. doi: 10.1016/j.jcmgh.2018.12.002

18. Zhang Z, Lu Y, Qi J, Wu W. An update on oral drug delivery via intestinal lymphatic transport. Acta Pharmaceutica Sinica B 2021; 11(8): 2449–2468. doi: 10.1016/j.apsb.2020.12.022

19. Bisgaier CL, Glickman RM. Intestinal synthesis, secretion, and transport of lipoproteins. Annual Review of Physiolog 1983; 45(1): 625–636. doi: 10.1146/annurev.ph.45.030183.003205

20. Ko CW, Qu J, Black DD, Tso P. Regulation of intestinal lipid metabolism: Current concepts and relevance to disease. Nature Reviews Gastroenterology and Hepatology 2020; 17(3): 169–183. doi: 10.1038/s41575-019-0250-7

21. Xiao C, Stahel P, Lewis GF. Regulation of chylomicron secretion: Focus on post-assembly mechanisms. Cellular and Molecular Gastroenterology and Hepatology 2019; 7(3): 487–501. doi: 10.1016/j.jcmgh.2018.10.015

22. Bickerton AS, Roberts R, Fielding BA, et al. Preferential uptake of dietary fatty acids in adipose tissue and muscle in the postprandial period. Diabetes 2007; 56(1): 168–176. doi: 10.2337/db06-0822

23. Voshol PJ, Rensen PCN, Van Dijk KW, et al. Effect of plasma triglyceride metabolism on lipid storage in adipose tissue: Studies using genetically engineered mouse models. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 2009; 1791(6): 479–485. doi: 10.1016/j.bbalip.2008.12.015

24. Cooper AD. Hepatic uptake of chylomicron remnants. Journal of Lipid Research 1997; 38(11): 2173–2192. doi: 10.1016/S0022-2275(20)34932-4

25. Zannis VI, Chroni A, Kypreos KE, et al. Probing the pathways of chylomicron and HDL metabolism using adenovirus-mediated gene transfer. Current Opinion in Lipidology 2004; 15(2): 151–166. doi: 10.1097/00041433-200404000-00008

26. Linton MF, Yancey PG, Davies SS, et al. The role of lipids and lipoproteins in atherosclerosis. Available online: https://www.ncbi.nlm.nih.gov/books/NBK343489/ (accessed on 30 August 2023).

27. Williams KJ. Molecular processes that handle—and mishandle—dietary lipids. Journal of Clinical Investigation 2008; 118(10): 3247–3259. doi: 10.1172/JCI35206

28. Yousef M, Park C, Le TS, et al. Simulated lymphatic fluid for in-vitro assessment in pharmaceutical development. Dissolution Technologies 2022; 29(2): 86–93. doi: 10.14227/DT290222P86

29. Solari E, Marcozzi C, Bartolini B, et al. Acute exposure of collecting lymphatic vessels to low-density lipoproteins increases both contraction frequency and lymph flow: An in vivo mechanical insight. Lymphatic Research and Biology 2020; 18(2): 146–155. doi: 10.1089/lrb.2019.0040

30. Huang LH, Elvington A, Randolph GJ. The role of the lymphatic system in cholesterol transport. Frontiers in Pharmacology 2015; 6: 182. doi: 10.3389/fphar.2015.00182

31. Vuorio T, Nurmi H, Moulton K, et al. Lymphatic vessel insufficiency in hypercholesterolemic mice alters lipoprotein levels and promotes atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology 2014; 34(6): 1162–1170. doi: 10.1161/ATVBAHA.114.302528

32. Rafieian-Kopaei M, Setorki M, Doudi M, et al. Atherosclerosis: Process, indicators, risk factors and new hopes. International Journal of Preventive Medicine 2014; 5(8): 927–946.

33. Gracia G, Cao E, Johnston APR, et al. Organ-specific lymphatics play distinct roles in regulating HDL trafficking and composition. American Journal of Physiology-Gastrointestinal and Liver Physiology 2020; 318(4): G725–G735. doi: 10.1152/ajpgi.00340.2019

34. Chakraborty S, Zawieja S, Wang W, et al. Lymphatic system: A vital link between metabolic syndrome and inflammation. Annals of the New York Academy of Sciences 2010; 1207: E94–102. doi: 10.1111/j.1749-6632.2010.05752.x

35. Charman WNA, Stella VJ. Estimating the maximal potential for intestinal lymphatic transport of lipophilic drug molecules. International Journal of Pharmaceutics 1986; 34(1–2): 175–178. doi: 10.1016/0378-5173(86)90027-X

36. Pandita D, Ahuja A, Lather V, et al. Development of lipid-based nanoparticles for enhancing the oral bioavailability of paclitaxel. AAPS PharmSciTech 2011; 12(2): 712–722. doi: 10.1208/s12249-011-9636-8

37. Maisel K, McClain CA, Bogseth A, Thomas SN. Nanotechnologies for physiology-informed drug delivery to the lymphatic system. Annual Review of Biomedical Engineering 2023; 25: 233–256. doi: 10.1146/annurev-bioeng-092222-034906




DOI: https://doi.org/10.24294/ace.v6i2.2202

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