Skip to main content
SpringerLink
Log in

Stimulation of phagocyte adhesion to endothelial cells by modified VLDL and HDL requires scavenger receptor BI

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Hyperglycemia- and oxidative stress-induced modification of circulating lipoproteins is being increasingly recognized as an important pathogenetic factor for diabetic cardiovascular damages. This study was designed to investigate the impact of modified very low-density lipoprotein and high-density lipoprotein on phagocyte adhesion to endothelial cells and the involvement of scavenger receptor class B type 1 (SR-BI) in this process. Native lipoproteins were isolated by density gradient ultracentrifugation and in vitro glycoxidative or oxidative modification was performed in the presence of glucose or sodium hypochlorite, respectively. One hour co-incubation experiments with lipoproteins, freshly prepared polymorphonuclear leukocytes (PMN), and venous endothelial cells (HUVEC) were performed in the presence or absence of different scavenger receptors and signal transduction inhibitors. PMN adhesion to HUVEC was quantified fluorimetrically. We demonstrated that oxidized and glycoxidized lipoproteins promote adhesion of PMN to HUVEC from 1.5- to 2.5-fold with oxidized lipoproteins having the greatest effect. Treatment with the highly specific SR-BI inhibitor, BLT-1 produced substantial reduction of lipoprotein-induced adhesion to endothelial cells. Native and modified lipoproteins recruited extracellular signal-regulated kinase (ERK 1/2), p38 mitogen-activated protein kinase, and Janus kinase 2 as downstream signaling pathways for adhesion. From this study, it could be concluded that modification of lipoproteins plays a crucial role in atherosclerotic progression and SR-BI may be considered as a potential therapeutic target for the prevention of diabetic cardiovascular complications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rader DJ, Daugherty A (2008) Translating molecular discoveries into new therapies for atherosclerosis. Nature 451:904–1913

    Article  PubMed  CAS  Google Scholar 

  2. Steinberg D (1997) Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272:20963–20966

    Article  PubMed  CAS  Google Scholar 

  3. Kopprasch S, Leonhardt W, Pietzsch J, Kuhne H (1998) Hypochlorite-modified low-density lipoprotein stimulates human polymorphonuclear leukocytes for enhanced production of reactive oxygen metabolites, enzyme secretion, and adhesion to endothelial cells. Atherosclerosis 136:315–324

    Article  PubMed  CAS  Google Scholar 

  4. Graessler J, Pietzsch J, Westendorf T, Julius U, Bornstein SR, Kopprasch S (2007) Glycoxidised LDL isolated from subjects with impaired glucose tolerance increases CD36 and peroxisome proliferator-activator receptor γ gene expression in macrophages. Diabetologia 50:1080–1088

    Article  PubMed  CAS  Google Scholar 

  5. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky RL, Mohler ER, Rothblat GH, Rader DJ (2011) Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med 364:127–135

    Article  PubMed  CAS  Google Scholar 

  6. Ramet ME, Ramet M, Lu Q, Nickerson M, Savolainen MJ, Malzone A, Karas RH (2003) High-density lipoprotein increases the abundance of eNOS protein in human vascular endothelial cells by increasing its half-life. J Am Coll Cardiol 41:2288–2297

    Article  PubMed  CAS  Google Scholar 

  7. Kimura T, Tomura H, Mogi C, Kuwabara A, Damirin A, Ishizuka T, Sekiguchi A, Ishiwara M, Im DS, Sato K, Murakami M, Okajima F (2006) Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells. J Biol Chem 281:37457–37467

    Article  PubMed  CAS  Google Scholar 

  8. Mineo C, Shaul PW (2007) Role of high-density lipoprotein and scavenger receptor B type I in the promotion of endothelial repair. Trends Cardiovasc Med 17:156–161

    Article  PubMed  CAS  Google Scholar 

  9. Zhu W, Saddar S, Seetharam D, Chambliss KL, Longoria C, Silver DL, Yuhanna IS, Shaul PW, Mineo C (2008) The scavenger receptor class B type I adaptor protein PDZK1 maintains endothelial monolayer integrity. Circ Res 102:480–487

    Article  PubMed  CAS  Google Scholar 

  10. Kopprasch S, Pietzsch J, Graessler J (2004) The protective effects of HDL and its constitutents against neutrophil respiratory burst activation by hypochlorite-oxidized LDL. Mol Cell Biochem 258(1–2):121–127

    Article  PubMed  CAS  Google Scholar 

  11. Kontush A, Chapman JM (2006) Functionally defective HDL: a new therapeutic target at the crossroads of dyslipidemia, inflammation and atherosclerosis. Pharmacol Rev 58:342–374

    Article  PubMed  CAS  Google Scholar 

  12. Adiels M, Olofsson SO, Taskinen MR, Boren J (2008) Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler Thromb Vasc Biol 28:1225–12236

    Article  PubMed  CAS  Google Scholar 

  13. Kawakami A, Aikawa M, Libby P, Alcaide P, Luscinskas FW, Sacks FM (2006) Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation 113:691–700

    Article  PubMed  CAS  Google Scholar 

  14. Chen C, Lu J, Chen S, Hung RY, Yilmaz HR, Dong J, Elayda MA, Dixon RAF, Yang C (2012) Effects of electronegative VLDL on endothelium damage in metabolic syndrome. Diabetes Care 35(3):648–653

    Article  PubMed  CAS  Google Scholar 

  15. Krieger M (2001) Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest 108:793–797

    PubMed  CAS  Google Scholar 

  16. Huszar D, Varban ML, Rinninger F, Feeley R, Arai T, Fairchild-Huntress V, Donovan MJ, Tall AR (2000) Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1. Arterioscler Thromb Vasc Biol 20:1068–1073

    Article  PubMed  CAS  Google Scholar 

  17. Pietzsch J, Subat S, Nitzsche S, Leonhardt W, Schentke KU, Hanefeld M (1995) Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein separation and composition. Biochim Biophys Acta 1254:77–88

    Article  PubMed  Google Scholar 

  18. Maeba R, Shimasaki H, Ueta N (1994) Conformational changes in oxidized LDL recognized by mouse peritoneal macrophages. Biochim Biophys Acta 1215:79–86

    Article  PubMed  CAS  Google Scholar 

  19. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

    Article  PubMed  CAS  Google Scholar 

  20. Yagi K (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15:212–216

    Article  PubMed  CAS  Google Scholar 

  21. Kopprasch S, Pietzsch J, Westendorf T, Kruse HJ, Graessler J (2004) The pivotal role of scavenger receptor CD36 and phagocyte-derived oxidants in oxidized low density lipoprotein-induced adhesion to endothelial cells. Int J Biochem Cell Biol 36:460–471

    Article  PubMed  CAS  Google Scholar 

  22. Nieland TJF, Penman M, Dori L, Krieger M, Kirchhausen T (2002) Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI. Proc Natl Acad Sci USA 99:15422–15427

    Article  PubMed  CAS  Google Scholar 

  23. Wang X, Greilberger J, Ledinski G, Kager G, Jurgens G (2001) Binding and uptake of differently oxidized low density lipoprotein in mouse peritoneal macrophages and THP-1 macrophages: involvement of negative charges as well as oxidation-specific epitopes. J Cell Biochem 81:557–569

    Article  PubMed  CAS  Google Scholar 

  24. Videm V, Albrigtsen M (2008) Soluble ICAM-1 and VCAM-1 as markers of endothelial activation. Scand J Immunol 67:523–531

    Article  PubMed  CAS  Google Scholar 

  25. Marcos V, Latzin P, Hector A, Sonanini S, Hoffmann F, Lacher M, Koller B, Bufler P, Nicolai T, Hartl D, Griese M (2010) Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases. Respir Res 19:11–32

    Google Scholar 

  26. Saha S, Willenberg HS, Bornstein SR, Graessler J, Kopprasch S (2011) Diabetic lipoproteins and adrenal aldosterone synthesis–a possible pathophysiological link? Horm Metab Res 44:239–244

    PubMed  Google Scholar 

  27. Saha S, Graessler J, Schwarz PEH, Goettsch C, Bornstein SR, Kopprasch S (2012) Modified high-density lipoprotein modulates aldosterone release through scavenger receptors via extra cellular signal-regulated kinase and Janus kinase-dependent pathways. Mol Cell Biochem 366:1–10

    Article  PubMed  CAS  Google Scholar 

  28. Chait A, Bornfeldt KE (2009) Diabetes and atherosclerosis: is there a role for hyperglycemia? J Lipid Res 50:S335–S339

    Article  PubMed  Google Scholar 

  29. Matsuda Y, Hirata K, Inoue N, Suematsu M, Kawashima S, Akita H, Yokoyama M (1993) High density lipoprotein reverses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation. Circ Res 72:1103–1109

    Article  PubMed  CAS  Google Scholar 

  30. Kozarsky KF, Donahee MH, Glick JM et al (2000) Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 20:721–727

    Article  PubMed  CAS  Google Scholar 

  31. Younis N, Charlton-Menys V, Sharma R, Soran H, Durrington PN (2009) Glycation of LDL in non-diabetic people: small dense LDL is preferentially glycated both in vivo and in vitro. Atherosclerosis 202:162–168

    Article  PubMed  CAS  Google Scholar 

  32. Nobecourt E, Tabet F, Lambert G, Puranik R, Bao S, Yan L, Davies MJ, Brown BE, Jenkins AJ, Dusting GJ, Bonnet DJ, Curtiss LK, Barter PJ, Rye KA (2010) Nonenzymatic glycation impairs the antiinflammatory properties of apolipoprotein A-I. Arterioscler Thromb Vasc Biol 30:766–772

    Article  PubMed  CAS  Google Scholar 

  33. Seger R, Krebs EG (1995) The MAPK signaling cascade. FASEB J 9:726–735

    PubMed  CAS  Google Scholar 

  34. Norata GD, Pirillo A, Callegari E, Hamsten A, Catapano AL, Eriksson P (2003) Gene expression and intracellular pathways involved in endothelial dysfunction induced by VLDL and oxidised VLDL. Cardiovasc Res 59:169–180

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Eva Schubert, Sigrid Nitzsche, and Martina Kohl for the excellent technical support.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Pathological Biochemistry, Department of Internal Medicine 3, Carl Gustav Carus Medical School, University of Technology Dresden, Fetscherstraße 74, 01307, Dresden, Germany

    Sarama Saha, Juergen Graessler, Stefan R. Bornstein, Peter E. H. Schwarz & Steffi Kopprasch

Authors
  1. Sarama Saha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juergen Graessler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan R. Bornstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter E. H. Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Steffi Kopprasch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steffi Kopprasch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saha, S., Graessler, J., Bornstein, S.R. et al. Stimulation of phagocyte adhesion to endothelial cells by modified VLDL and HDL requires scavenger receptor BI. Mol Cell Biochem 383, 21–28 (2013). https://doi.org/10.1007/s11010-013-1749-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1749-9

Keywords

Search

Navigation