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Open Access 01-06-2011

Role of Hepatic Lipase and Endothelial Lipase in High-Density Lipoprotein—Mediated Reverse Cholesterol Transport

Authors: Wijtske Annema, Uwe J. F. Tietge

Published in: Current Atherosclerosis Reports | Issue 3/2011

Abstract

Reverse cholesterol transport (RCT) constitutes a key part of the atheroprotective properties of high-density lipoproteins (HDL). Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol levels. Although overexpression of EL decreases overall macrophage-to-feces RCT, knockout of both HL and EL leaves RCT essentially unaffected. With respect to important individual steps of RCT, current data on the role of EL and HL in cholesterol efflux are not conclusive. Both enzymes increase hepatic selective cholesterol uptake; however, this does not translate into altered biliary cholesterol secretion, which is regarded the final step of RCT. Also, the impact of HL and EL on atherosclerosis is not clear cut; rather it depends on respective experimental conditions and chosen models. More mechanistic insights into the diverse biological properties of these enzymes are therefore required to firmly establish EL and HL as targets for the treatment of atherosclerotic cardiovascular disease.

Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.PubMedCrossRef

Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res. 2005;96:1221–32.PubMedCrossRef

Yasuda T, Ishida T, Rader DJ. Update on the role of endothelial lipase in high-density lipoprotein metabolism, reverse cholesterol transport, and atherosclerosis. Circ J. 2010;74:2263–70.PubMedCrossRef

Santamarina-Fojo S, Gonzalez-Navarro H, Freeman L, et al. Hepatic lipase, lipoprotein metabolism, and atherogenesis. Arterioscler Thromb Vasc Biol. 2004;24:1750–4.PubMedCrossRef

Jin W, Marchadier D, Rader DJ. Lipases and HDL metabolism. Trends Endocrinol Metab. 2002;13:174–8.PubMedCrossRef

• Brown RJ, Lagor WR, Sankaranaravanan S, et al. Impact of combined deficiency of hepatic lipase and endothelial lipase on the metabolism of both high-density lipoproteins and apolipoprotein B-containing lipoproteins. Circ Res. 2010;107:357–64. This is the first article determining the role of hepatic lipase and endothelial lipase knockout and hepatic lipase/endothelial lipase double-knockout on macrophage-to-feces reverse cholesterol transport. PubMedCrossRef

Ruel IL, Couture P, Cohn JS, et al. Evidence that hepatic lipase deficiency in humans is not associated with proatherogenic changes in HDL composition and metabolism. J Lipid Res. 2004;45:1528–37.PubMedCrossRef

Johannsen TH, Kamstrup PR, Andersen RV, et al. Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease. J Clin Endocrinol Metab. 2009;94:1264–73.PubMedCrossRef

Isaacs A, Sayed-Tabatabaei FA, Njajou OT, et al. The −514C- >T hepatic lipase promoter region polymorphism and plasma lipids: a meta-analysis. J Clin Endocrinol Metab. 2004;89:3858–63.PubMedCrossRef

10.

Amigo L, Mardones P, Ferrada C, et al. Biliary lipid secretion, bile acid metabolism, and gallstone formation are not impaired in hepatic lipase-deficient mice. Hepatology. 2003;38:726–34.PubMedCrossRef

11.

Barcat D, Amadio A, Palos-Pinto A, et al. Combined hyperlipidemia/ hyperalphalipoproteinemia associated with premature spontaneous atherosclerosis in mice lacking hepatic lipase and low density lipoprotein receptor. Atherosclerosis. 2006;188:347–55.PubMedCrossRef

12.

Dichek HL, Qian K, Agrawal N. The bridging function of hepatic lipase clears plasma cholesterol in LDL receptor-deficient “apoB-48-only” and “apoB-100-only” mice. J Lipid Res. 2004;45:551–60.PubMedCrossRef

13.

Freeman L, Amar MJ, Shamburek R, et al. Lipolytic and ligand-binding functions of hepatic lipase protect against atherosclerosis in LDL receptor-deficient mice. J Lipid Res. 2007;48:104–13.PubMedCrossRef

14.

Qian K, Agrawal N, Dichek HL. Reduced atherosclerosis in chow-fed mice expressing high levels of a catalytically inactive human hepatic lipase. Atherosclerosis. 2007;195:66–74.PubMedCrossRef

15.

Mezdour H, Jones R, Dengremont C, et al. Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility to atherosclerosis in apolipoprotein E-deficient mice. J Biol Chem. 1997;272:13570–5.PubMedCrossRef

16.

Karackattu SL, Trigatti B, Krieger M. Hepatic lipase deficiency delays atherosclerosis, myocardial infarction, and cardiac dysfunction and extends lifespan in SR-BI/apolipoprotein E double knockout mice. Arterioscler Thromb Vasc Biol. 2006;26:548–54.PubMedCrossRef

17.

Nong Z, Gonzalez-Navarro H, Amar M, et al. Hepatic lipase expression in macrophages contributes to atherosclerosis in apoE-deficient and LCAT-transgenic mice. J Clin Invest. 2003;112:367–78.PubMed

18.

Hime NJ, Black AS, Bulgrien JJ, Curtiss LK. Leukocyte-derived hepatic lipase increases HDL and decreases en face aortic atherosclerosis in LDLr−/− mice expressing CETP. J Lipid Res. 2008;49:2113–23.PubMedCrossRef

19.

Hegele RA, Little JA, Vezina C, et al. Hepatic lipase deficiency. Clinical, biochemical, and molecular genetic characteristics. Arterioscler Thromb. 1993;13:720–8.PubMed

20.

Dugi KA, Brandauer K, Schmidt N, et al. Low hepatic lipase activity is a novel risk factor for coronary artery disease. Circulation. 2001;104:3057–62.PubMedCrossRef

21.

Fan YM, Lehtimaki T, Rontu R, et al. The hepatic lipase gene C-480T polymorphism in the development of early coronary atherosclerosis: the Helsinki Sudden Death Study. Eur J Clin Invest. 2007;37:472–7.PubMedCrossRef

22.

Andersen RV, Wittrup HH, Tybjaerg-Hansen A, et al. Hepatic lipase mutations, elevated high-density lipoprotein cholesterol, and increased risk of ischemic heart disease: the Copenhagen City Heart Study. J Am Coll Cardiol. 2003;41:1972–82.PubMedCrossRef

23.

Ji J, Herbison CE, Mamotte CD, et al. Hepatic lipase gene −514C/T polymorphism and premature coronary heart disease. J Cardiovasc Risk. 2002;9:105–13.PubMedCrossRef

24.

Shohet RV, Vega GL, Anwar A, et al. Hepatic lipase (LIPC) promoter polymorphism in men with coronary artery disease. Allele frequency and effects on hepatic lipase activity and plasma HDL-C concentrations. Arterioscler Thromb Vasc Biol. 1999;19:1975–8.PubMed

25.

Rundek T, Elkind MS, Pittman J, et al. Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study. Stroke. 2002;33:1420–3.PubMedCrossRef

26.

Hirata K, Dichek HL, Cioffi JA, et al. Cloning of a unique lipase from endothelial cells extends the lipase gene family. J Biol Chem. 1999;274:14170–5.PubMedCrossRef

27.

Jaye M, Lynch KJ, Krawiec J, et al. A novel endothelial-derived lipase that modulates HDL metabolism. Nat Genet. 1999;21:424–8.PubMedCrossRef

28.

• Nijstad N, Wiersma H, Gautier T, et al. Scavenger receptor BI-mediated selective uptake is required for the remodeling of high density lipoprotein by endothelial lipase. J Biol Chem. 2009;284:6093–100. This is a comprehensive study including HDL kinetics to demonstrate the complex interaction between EL, HDL, and the SR-BI. PubMedCrossRef

29.

Maugeais C, Tietge UJF, Broedl UC, et al. Dose-dependent acceleration of high-density lipoprotein catabolism by endothelial lipase. Circulation. 2003;108:2121–6.PubMedCrossRef

30.

Wiersma H, Gatti A, Nijstad N, et al. Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice. J Lipid Res. 2009;50:1571–80.PubMedCrossRef

31.

Badellino KO, Wolfe ML, Reilly MP, Rader DJ. Endothelial lipase concentrations are increased in metabolic syndrome and associated with coronary atherosclerosis. PLoS Med. 2006;3:e22.PubMedCrossRef

32.

Yamakawa-Kobayashi K, Yanagi H, Endo K, et al. Relationship between serum HDL-C levels and common genetic variants of the endothelial lipase gene in Japanese school-aged children. Hum Genet. 2003;113:311–5.PubMedCrossRef

33.

Mank-Seymour AR, Durham KL, Thompson JF, et al. Association between single-nucleotide polymorphisms in the endothelial lipase (LIPG) gene and high-density lipoprotein cholesterol levels. Biochim Biophys Acta. 2004;1636:40–6.PubMed

34.

•• Edmondson AC, Brown RJ, Kathiresan S, et al. Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J Clin Invest. 2009;119:1042–50. This is an important study demonstrating that endothelial lipase is a negative regulator of HDL plasma levels in humans using an experimental approach that combines human genetics with in vitro work and proof-of-concept studies in experimental animals. PubMed

35.

Brown RJ, Edmondson AC, Griffon N, et al. A naturally occurring variant of endothelial lipase associated with elevated HDL exhibits impaired synthesis. J Lipid Res. 2009;50:1910–6.PubMedCrossRef

36.

Paradis ME, Couture P, Bosse Y, et al. The T111I mutation in the EL gene modulates the impact of dietary fat on the HDL profile in women. J Lipid Res. 2003;44:1902–8.PubMedCrossRef

37.

Halverstadt A, Phares DA, Ferrell RE, et al. High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype. Metabolism. 2003;52:1505–11.PubMedCrossRef

38.

Qiu G, Hill JS. Endothelial lipase promotes apolipoprotein AI-mediated cholesterol efflux in THP-1 macrophages. Arterioscler Thromb Vasc Biol. 2009;29:84–91.PubMedCrossRef

39.

Gauster M, Oskolkova OV, Innerlohinger J, et al. Endothelial lipase-modified high-density lipoprotein exhibits diminished ability to mediate SR-BI (scavenger receptor B type I)-dependent free-cholesterol efflux. Biochem J. 2004;382:75–82.PubMedCrossRef

40.

Yancey PG, Kawashiri MA, Moore R, et al. In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1-mediated cholesterol efflux. J Lipid Res. 2004;45:337–46.PubMedCrossRef

41.

Strauss JG, Zimmermann R, Hrzenjak A, et al. Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity. Biochem J. 2002;368:69–79.PubMedCrossRef

42.

Jin W, Wang X, Millar JS, et al. Hepatic proprotein convertases modulate HDL metabolism. Cell Metab. 2007;6:129–36.PubMedCrossRef

43.

Ishida T, Choi SY, Kundu RK, et al. Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein-E-deficient mice. J Biol Chem. 2004;279:45085–92.PubMedCrossRef

44.

Ko KW, Paul A, Ma K, et al. Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE−/− and LDLR−/− mice. J Lipid Res. 2005;46:2586–94.PubMedCrossRef

45.

van der Giet M, Tolle M, Pratico D, et al. Increased type IIA secretory phospholipase A(2) expression contributes to oxidative stress in end-stage renal disease. J Mol Med. 2010;88:75–83.PubMedCrossRef

46.

Fujii H, Fukuda A, Tanaka M, et al. Putative role of endothelial lipase in dialysis patients with hypoalbuminemia and inflammation. Am J Nephrol. 2008;28:974–81.PubMedCrossRef

47.

Shimizu M, Kanazawa K, Hirata K, et al. Endothelial lipase gene polymorphism is associated with acute myocardial infarction, independently of high-density lipoprotein-cholesterol levels. Circ J. 2007;71:842–6.PubMedCrossRef

48.

Tang NP, Wang LS, Yang L, et al. Protective effect of an endothelial lipase gene variant on coronary artery disease in a Chinese population. J Lipid Res. 2008;49:369–75.PubMedCrossRef

49.

Jensen MK, Rimm EB, Mukamal KJ, et al. The T111I variant in the endothelial lipase gene and risk of coronary heart disease in three independent populations. Eur Heart J. 2009;30:1584–9.PubMedCrossRef

50.

Vergeer M, Cohn DM, Boekholdt SM, et al. Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT. Atherosclerosis. 2010;211:558–64.PubMedCrossRef

Title: Role of Hepatic Lipase and Endothelial Lipase in High-Density Lipoprotein—Mediated Reverse Cholesterol Transport
Authors: Wijtske Annema
Uwe J. F. Tietge
Publication date: 01-06-2011
Publisher: Current Science Inc.
Published in: Current Atherosclerosis Reports / Issue 3/2011
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-011-0175-2

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