Skip to main content
SpringerLink
Log in

HDL and Sepsis

  • Chapter
  • First Online:
HDL Metabolism and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1377))

Abstract

Sepsis has been recognized as a global health burden in the year 2017 for its high morbidity and mortality. HDL, a cholesterol transporter, also plays vital role in inflammation besides its typical role in reverse cholesterol transportation. In septic patients, HDL levels dropped significantly. HDL exerts a variety of protective effects in the pathophysiology of sepsis including acting on pathogens, inhibiting macrophage inflammatory reaction, and modulating endothelial function in sepsis. Studies have shown that rHDL or apoA-I mimetic peptides could be therapeutic potentials in sepsis. HDL has caused increasing concern as a potential therapeutic agent.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Reinhart K et al (2017) Recognizing sepsis as a Global Health priority - a WHO resolution. N Engl J Med 377(5):414–417

    Article  PubMed  Google Scholar 

  2. Angus DC et al (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29(7):1303–1310

    Article  CAS  PubMed  Google Scholar 

  3. Mayr FB, Yende S, Angus DC (2014) Epidemiology of severe sepsis. Virulence 5(1):4–11

    Article  PubMed  Google Scholar 

  4. Fleischmann C et al (2016) Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 193(3):259–272

    Article  CAS  PubMed  Google Scholar 

  5. Singer M et al (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315(8):801–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Angus DC, van der Poll T (2013) Severe sepsis and septic shock. N Engl J Med 369(9):840–851

    Article  CAS  PubMed  Google Scholar 

  7. Vincent JL et al (2006) Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 34(2):344–353

    Article  PubMed  Google Scholar 

  8. Vincent JL et al (2014) Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit. Lancet Respir Med 2(5):380–386

    Article  PubMed  Google Scholar 

  9. Vincent JL et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302(21):2323–2329

    Article  CAS  PubMed  Google Scholar 

  10. Karlsson S et al (2007) Incidence, treatment, and outcome of severe sepsis in ICU-treated adults in Finland: the Finnsepsis study. Intensive Care Med 33(3):435–443

    Article  PubMed  Google Scholar 

  11. Boyd JH, Russell JA, Fjell CD (2014) The meta-genome of sepsis: host genetics, pathogens and the acute immune response. J Innate Immun 6(3):272–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348(2):138–150

    Article  CAS  PubMed  Google Scholar 

  13. Cecconi M et al (2018) Sepsis and septic shock. Lancet 392(10141):75–87

    Article  PubMed  Google Scholar 

  14. Ferrer R et al (2014) Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 42(8):1749–1755

    Article  CAS  PubMed  Google Scholar 

  15. Garnacho-Montero J et al (2008) Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICU with sepsis: a matched cohort study. J Antimicrob Chemother 61(2):436–441

    Article  CAS  PubMed  Google Scholar 

  16. Ibrahim EH et al (2000) The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 118(1):146–155

    Article  CAS  PubMed  Google Scholar 

  17. van Leeuwen HJ et al (2003) Lipoprotein metabolism in patients with severe sepsis. Crit Care Med 31(5):1359–1366

    Article  PubMed  CAS  Google Scholar 

  18. Tanaka S et al (2017) Low HDL levels in sepsis versus trauma patients in intensive care unit. Ann Intensive Care 7(1):60

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Chien JY et al (2005) Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit Care Med 33(8):1688–1693

    Article  CAS  PubMed  Google Scholar 

  20. Barlage S et al (2009) Changes in HDL-associated apolipoproteins relate to mortality in human sepsis and correlate to monocyte and platelet activation. Intensive Care Med 35(11):1877–1885

    Article  CAS  PubMed  Google Scholar 

  21. Genga KR et al (2018) CETP genetic variant rs1800777 (allele A) is associated with abnormally low HDL-C levels and increased risk of AKI during sepsis. Sci Rep 8(1):16764

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Cirstea M et al (2017) Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis. J Crit Care 38:289–294

    Article  CAS  PubMed  Google Scholar 

  23. Pirillo A, Catapano AL, Norata GD (2019) Biological consequences of dysfunctional HDL. Curr Med Chem 26(9):1644–1664

    Article  CAS  PubMed  Google Scholar 

  24. Guirgis FW et al (2018) HDL cholesterol efflux is impaired in older patients with early sepsis: a subanalysis of a prospective pilot study. Shock 50(1):66–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Guirgis FW et al (2017) Exploring the predictive ability of dysfunctional high-density lipoprotein for adverse outcomes in emergency department patients with sepsis: a preliminary investigation. Shock 48(5):539–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Guirgis FW et al (2016) Cholesterol levels and long-term rates of community-acquired sepsis. Crit Care 20(1):408

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rall DP, Gaskins JR, Kelly MG (1957) Reduction of febrile response to bacterial polysaccharide following incubation with serum. Am J Phys 188(3):559–562

    Article  CAS  Google Scholar 

  28. Ulevitch RJ, Johnston AR, Weinstein DB (1979) New function for high density lipoproteins. Their participation in intravascular reactions of bacterial lipopolysaccharides. J Clin Invest 64(5):1516–1524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ulevitch RJ, Johnston AR, Weinstein DB (1981) New function for high density lipoproteins. Isolation and characterization of a bacterial lipopolysaccharide-high density lipoprotein complex formed in rabbit plasma. J Clin Invest 67(3):827–837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Flegel WA et al (1989) Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins. Infect Immun 57(7):2237–2245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Dai L et al (2010) The apolipoprotein A-I mimetic peptide 4F prevents defects in vascular function in endotoxemic rats. J Lipid Res 51(9):2695–2705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lamping N et al (1998) LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria. J Clin Invest 101(10):2065–2071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vesy CJ et al (2000) Lipopolysaccharide-binding protein and phospholipid transfer protein release lipopolysaccharides from gram-negative bacterial membranes. Infect Immun 68(5):2410–2417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Levels JH et al (2005) Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect Immun 73(4):2321–2326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cohen J (1999) Adjunctive therapy in sepsis: a critical analysis of the clinical trial programme. Br Med Bull 55(1):212–225

    Article  CAS  PubMed  Google Scholar 

  36. Hoekstra M, Sorci-Thomas M (2017) Rediscovering scavenger receptor type BI: surprising new roles for the HDL receptor. Curr Opin Lipidol 28(3):255–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cai L et al (2008) SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance. J Clin Invest 118(1):364–375

    Article  CAS  PubMed  Google Scholar 

  38. Vishnyakova TG et al (2003) Binding and internalization of lipopolysaccharide by Cla-1, a human orthologue of rodent scavenger receptor B1. J Biol Chem 278(25):22771–22780

    Article  CAS  PubMed  Google Scholar 

  39. De Kimpe SJ et al (1995) The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure. Proc Natl Acad Sci U S A 92(22):10359–10363

    Article  PubMed  PubMed Central  Google Scholar 

  40. Levels JH et al (2003) Distribution and kinetics of lipoprotein-bound lipoteichoic acid. Infect Immun 71(6):3280–3284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Grunfeld C et al (1999) Lipoproteins inhibit macrophage activation by lipoteichoic acid. J Lipid Res 40(2):245–252

    Article  CAS  PubMed  Google Scholar 

  42. Jiao YL, Wu MP (2008) Apolipoprotein A-I diminishes acute lung injury and sepsis in mice induced by lipoteichoic acid. Cytokine 43(1):83–87

    Article  CAS  PubMed  Google Scholar 

  43. Kumar V (2018) Targeting macrophage immunometabolism: Dawn in the darkness of sepsis. Int Immunopharmacol 58:173–185

    Article  CAS  PubMed  Google Scholar 

  44. De Nardo D et al (2014) High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol 15(2):152–160

    Article  PubMed  CAS  Google Scholar 

  45. Huang J et al (2018) AMPK regulates immunometabolism in sepsis. Brain Behav Immun 72:89–100

    Article  CAS  PubMed  Google Scholar 

  46. Vachharajani VT et al (2014) SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome. J Leukoc Biol 96(5):785–796

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Feig JE et al (2011) HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells. Proc Natl Acad Sci U S A 108(17):7166–7171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cockerill GW et al (1995) High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 15(11):1987–1994

    Article  CAS  PubMed  Google Scholar 

  49. McDonald MC et al (2003) Reconstituted high-density lipoprotein attenuates organ injury and adhesion molecule expression in a rodent model of endotoxic shock. Shock 20(6):551–557

    Article  CAS  PubMed  Google Scholar 

  50. Park SH et al (2003) Involvement of transcription factors in plasma HDL protection against TNF-alpha-induced vascular cell adhesion molecule-1 expression. Int J Biochem Cell Biol 35(2):168–182

    Article  CAS  PubMed  Google Scholar 

  51. Yuhanna IS et al (2001) High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med 7(7):853–857

    Article  CAS  PubMed  Google Scholar 

  52. Mineo C et al (2003) High density lipoprotein-induced endothelial nitric-oxide synthase activation is mediated by Akt and MAP kinases. J Biol Chem 278(11):9142–9149

    Article  CAS  PubMed  Google Scholar 

  53. Martin G et al (2014) Endothelial (NOS3 E298D) and inducible (NOS2 exon 22) nitric oxide synthase polymorphisms, as well as plasma NOx, influence sepsis development. Nitric Oxide 42:79–86

    Article  CAS  PubMed  Google Scholar 

  54. Spiller F et al (2019) Targeting nitric oxide as a key modulator of sepsis, arthritis and pain. Nitric Oxide 89:32–40

    Article  CAS  PubMed  Google Scholar 

  55. Norata GD et al (2004) HDL3 induces cyclooxygenase-2 expression and prostacyclin release in human endothelial cells via a p38 MAPK/CRE-dependent pathway: effects on COX-2/PGI-synthase coupling. Arterioscler Thromb Vasc Biol 24(5):871–877

    Article  CAS  PubMed  Google Scholar 

  56. Liu D et al (2011) Human apolipoprotein A-I induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through ATP-binding cassette transporter A1. Am J Physiol Cell Physiol 301(3):C739–C748

    Article  CAS  PubMed  Google Scholar 

  57. Zhang QH et al (2012) An involvement of SR-B1 mediated PI3K-Akt-eNOS signaling in HDL-induced cyclooxygenase 2 expression and prostacyclin production in endothelial cells. Biochem Biophys Res Commun 420(1):17–23

    Article  CAS  PubMed  Google Scholar 

  58. Viswambharan H et al (2004) Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase. Circ Res 94(7):918–925

    Article  CAS  PubMed  Google Scholar 

  59. Guo L et al (2013) High density lipoprotein protects against polymicrobe-induced sepsis in mice. J Biol Chem 288(25):17947–17953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yan YJ et al (2006) Beneficial effects of ApoA-I on LPS-induced acute lung injury and endotoxemia in mice. Life Sci 79(2):210–215

    Article  CAS  PubMed  Google Scholar 

  61. Parolini C (2020) A compendium of the biological effects of apolipoprotein A-IMilano. J Pharmacol Exp Ther 372(1):54–62

    Article  CAS  PubMed  Google Scholar 

  62. Zhang X, Wang L, Chen B (2015) Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction. Biol Chem 396(1):53–60

    Article  CAS  PubMed  Google Scholar 

  63. Levine DM et al (1993) In vivo protection against endotoxin by plasma high density lipoprotein. Proc Natl Acad Sci U S A 90(24):12040–12044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhang Z et al (2009) Apolipoprotein A-I mimetic peptide treatment inhibits inflammatory responses and improves survival in septic rats. Am J Physiol Heart Circ Physiol 297(2):H866–H873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Moreira RS et al (2014) Apolipoprotein A-I mimetic peptide 4F attenuates kidney injury, heart injury, and endothelial dysfunction in sepsis. Am J Physiol Regul Integr Comp Physiol 307(5):R514–R524

    Article  CAS  PubMed  Google Scholar 

  66. Kwon WY et al (2012) 4F, apolipoprotein AI mimetic peptide, attenuates acute lung injury and improves survival in endotoxemic rats. J Trauma Acute Care Surg 72(6):1576–1583

    Article  CAS  PubMed  Google Scholar 

  67. Tanaka S et al (2020) Reconstituted high-density lipoprotein therapy improves survival in mouse models of sepsis. Anesthesiology 132(4):825–838

    Article  CAS  PubMed  Google Scholar 

  68. Pajkrt D et al (1996) Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med 184(5):1601–1608

    Article  CAS  PubMed  Google Scholar 

  69. Pajkrt D et al (1997) Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia. Thromb Haemost 77(2):303–307

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing, China

    Huanhuan Cao

  2. Department of Cardiology, Chinese PLA Central War Command General Hospital, Wuhan, China

    Wei Huang

  3. Division of Cardiology, Department of Internal Medicine, and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Wei Huang

Authors
  1. Huanhuan Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences, Peking University, Beijing, China

    Lemin Zheng

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cao, H., Huang, W. (2022). HDL and Sepsis. In: Zheng, L. (eds) HDL Metabolism and Diseases. Advances in Experimental Medicine and Biology, vol 1377. Springer, Singapore. https://doi.org/10.1007/978-981-19-1592-5_10

Download citation

Publish with us

Policies and ethics

Search

Navigation