Elevated serum levels of lipoprotein‑associated phospholipase A2 predict mortality rates in patients with sepsis

Huang,Zhongwei; Jiang,Haiyan; Cui,Xiaohui; Liang,Guiwen; Chen,Yu; Wang,Ting; Sun,Zhichao; Qi,Lei

doi:10.3892/mmr.2017.8034

Elevated serum levels of lipoprotein‑associated phospholipase A2 predict mortality rates in patients with sepsis

Authors:
- Zhongwei Huang
- Haiyan Jiang
- Xiaohui Cui
- Guiwen Liang
- Yu Chen
- Ting Wang
- Zhichao Sun
- Lei Qi
View Affiliations

Affiliations: Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Geriatric Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Medical College, Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: November 13, 2017 https://doi.org/10.3892/mmr.2017.8034
Pages: 1791-1798

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sepsis remains one of the leading contributors to mortality rates in the intensive care unit (ICU) and emergency intensive care unit (EICU). Therefore, any treatments against the agents which produce sepsis in a medical emergency, are welcome. Elevated serum levels of lipoprotein‑associated phospholipase A2 (Lp‑PLA2) have been reported in a small cohort of patients with inflammation. The present study evaluated serum levels of Lp‑PLA2 in patients with sepsis and investigated the role of Lp‑PLA2 in sepsis. The investigation involved the selection of 151 patients with sepsis admitted to the emergency department of the Affiliated Hospital of Nantong University (Nantong, China) and 30 healthy controls. All patients (39 with sepsis, 55 with severe sepsis and 57 with septic shock) were examined on admission to the EICU. A complete blood count was performed, and serum levels of Lp‑PLA2, C‑reactive protein, procalcitonin, and interleukin 6, sequential organ failure (SOFA) scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were determined on hospital admission. The EICU and overall mortality rates were evaluated at baseline. The present study also assessed various laboratory parameters, clinical data and inflammatory cytokines. The patient follow up duration was 90 days. The data suggested that the serum levels of Lp‑PLA2 on admission to the EICU in patients with sepsis were elevated, compared with those in healthy controls. The concentrations of Lp‑PLA2 were correlated with the severity of disease, and were significantly associated with experimental markers of inflammation and established prognostic scores. In the total cohort, persistently elevated levels of Lp‑PLA2 on admission for EICU treatment was a predictor of poor prognosis, and provided superior diagnostic use, compared with the prognostic scoring systems, including SOFA or APACHE II scores. Taken together, the results suggested that Lp‑PLA2, with respect to other markers of inflammation, may have a role as a prognostic marker in sepsis, and provide background evidence for further trials to evaluate the clinical and pathophysiologic roles of Lp‑PLA2 in sepsis. Persistently elevated serum concentrations of Lp‑PLA2 indicated an unfavorable outcome in patients with sepsis. In addition, the results indicated the potential role of Lp‑PLA2 as a prognostic biomarker in patients with sepsis during the early course of EICU treatment.

View Figures

View References

1	Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C and Remick DG: Sepsis: Multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 93:1247–1288. 2013. View Article : Google Scholar :
2	Edman-Wallér J, Ljungström L, Jacobsson G, Andersson R and Werner M: Systemic symptoms predict presence or development of severe sepsis and septic shock. Infect Dis (Lond). 48:209–214. 2016. View Article : Google Scholar
3	Mayeux PR and MacMillan-Crow LA: Pharmacological targets in the renal peritubular microenvironment: Implications for therapy for sepsis-induced acute kidney injury. Pharmacol Ther. 134:139–155. 2012. View Article : Google Scholar :
4	Gill SE, Taneja R, Rohan M, Wang L and Mehta S: Pulmonary microvascular albumin leak is associated with endothelial cell death in murine sepsis-induced lung injury in vivo. PLoS One. 9:e885012014. View Article : Google Scholar :
5	Crouser E, Exline M, Knoell D and Wewers MD: Sepsis: Links between pathogen sensing and organ damage. Curr Pharm Des. 14:1840–1852. 2008. View Article : Google Scholar :
6	de Pablo R, Monserrat J, Prieto A and Alvarez-Mon M: Role of circulating lymphocytes in patients with sepsis. Biomed Res Int. 2014:6710872014. View Article : Google Scholar :
7	Hotchkiss RS and Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med. 348:138–150. 2003. View Article : Google Scholar
8	Sakr Y, Vincent JL, Ruokonen E, Pizzamiglio M, Installe E, Reinhart K and Moreno R: Sepsis Occurrence in Acutely Ill Patients Investigators: Sepsis and organ system failure are major determinants of post-intensive care unit mortality. J Crit Care. 23:475–483. 2008. View Article : Google Scholar
9	Yende S, Waterer GW, Tolley EA, Newman AB, Bauer DC, Taaffe DR, Jensen R, Crapo R, Rubin S, Nevitt M, et al: Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax. 61:10–16. 2006. View Article : Google Scholar
10	Najafi A, Mojtahedzadeh M, Ahmadi KH, Abdollahi M, Mousavi M, Chelkeba L, Najmeddin F and Ahmadi A: The immunological benefit of higher dose N-acetyl cysteine following mechanical ventilation in critically ill patients. Daru. 22:572014. View Article : Google Scholar :
11	Yende S, D'Angelo G, Mayr F, Kellum JA, Weissfeld L, Kaynar AM, Young T, Irani K and Angus DC: GenIMS Investigators: Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths. PLoS One. 6:e228472011. View Article : Google Scholar :
12	Moon SH, Jenkins CM, Liu X, Guan S, Mancuso DJ and Gross RW: Activation of mitochondrial calcium-independent phospholipase A2γ (iPLA2γ) by divalent cations mediating arachidonate release and production of downstream eicosanoids. J Biol Chem. 287:14880–14895. 2012. View Article : Google Scholar :
13	Dennis EA, Cao J, Hsu YH, Magrioti V and Kokotos G: Phospholipase A2 enzymes: Physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention. Chem Rev. 111:6130–6185. 2011. View Article : Google Scholar :
14	Stafforini DM, Elstad MR, McIntyre TM, Zimmerman GA and Prescott SM: Human macrophages secret platelet-activating factor acetylhydrolase. J Biol Chem. 265:9682–9687. 1990.
15	Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA, et al: Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature. 374:549–553. 1995. View Article : Google Scholar
16	Kudo I and Murakami M: Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 68–69:3–58. 2002. View Article : Google Scholar
17	Menschikowski M, Hagelgans A and Siegert G: Secretory phospholipase A2 of group IIA: Is it an offensive or a defensive player during atherosclerosis and other inflammatory diseases? Prostaglandins Other Lipid Mediat. 79:1–33. 2006. View Article : Google Scholar
18	Nevalainen TJ, Graham GG and Scott KF: Antibacterial actions of secreted phospholipases A2. Review. Biochim Biophys Acta. 1781:1–9. 2008. View Article : Google Scholar
19	Karabina SA, Gora S, Atout R and Ninio E: Extracellular phospholipases in atherosclerosis. Biochimie. 92:594–600. 2010. View Article : Google Scholar
20	Rosenson RS: Phospholipase A2 inhibition and atherosclerotic vascular disease: Prospects for targeting secretory and lipoprotein-associated phospholipase A2 enzymes. Curr Opin Lipidol. 21:473–480. 2010. View Article : Google Scholar
21	Suckling K: Phospholipase A2s: Developing drug targets for atherosclerosis. Atherosclerosis. 212:357–366. 2010. View Article : Google Scholar
22	Passacquale G, Di Giosia P and Ferro A: The role of inflammatory biomarkers in developing targeted cardiovascular therapies: Lessons from the cardiovascular inflammation reduction trials. Cardiovasc Res. 109:9–23. 2016. View Article : Google Scholar
23	Rosenson RS and Stafforini DM: Modulation of oxidative stress, inflammation, and atherosclerosis by lipoprotein-associated phospholipase A2. J Lipid Res. 53:1767–1782. 2012. View Article : Google Scholar :
24	Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, et al: International union of basic and clinical pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev. 66:1–79. 2013. View Article : Google Scholar
25	Kones R: Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: Relationship with subclinical disease, undertreatment, and poor adherence: Implications of new evidence upon optimizing cardiovascular patient outcomes. Vasc Health Risk Manag. 9:617–670. 2013. View Article : Google Scholar :
26	Zalewski A, Macphee C and Nelson JJ: Lipoprotein-associated phospholipase A2: A potential therapeutic target for atherosclerosis. Curr Drug Targets Cardiovasc Haematol Disord. 5:527–532. 2005. View Article : Google Scholar
27	Macphee CH, Nelson J and Zalewski A: Role of lipoprotein-associated phospholipase A2 in atherosclerosis and its potential as a therapeutic target. Curr Opin Pharmacol. 6:154–161. 2006. View Article : Google Scholar
28	Bedirli A, Gokahmetoglu S, Sakrak O, Soyuer I, Ince O and Sozuer E: Beneficial effects of recombinant platelet-activating factor acetylhydrolase and BN 52021 on bacterial translocation in cerulein-induced pancreatitis. Eur Surg Res. 36:136–141. 2004. View Article : Google Scholar
29	Onyimba JA, Coronado MJ, Garton AE, Kim JB, Bucek A, Bedja D, Gabrielson KL, Guilarte TR and Fairweather D: The innate immune response to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice. Biol Sex Differ. 2:22011. View Article : Google Scholar :
30	Hutchings L, Watkinson P, Young JD and Willett K: Defining multiple organ failure after major trauma: A comparison of the Denver, Sequential Organ Failure Assessment, and Marshall scoring systems. J Trauma Acute Care Surg. 82:534–541. 2017. View Article : Google Scholar :
31	Shrestha GS, Kwizera A, Lundeg G, Baelani JI, Azevedo LCP, Pattnaik R, Haniffa R, Gavrilovic S, Mai NTH, Kissoon N, et al: International Surviving Sepsis Campaign guidelines 2016: The perspective from low-income and middle-income countries. Lancet Infect Dis. 17:893–895. 2017. View Article : Google Scholar
32	Angstwurm MW, Dempfle CE and Spannagl M: New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores. Crit Care Med. 314–320; quiz 328. 2006. View Article : Google Scholar
33	Kojima M, Aiboshi J, Shibata M, Kobayashi T and Otomo Y: Novel role of group VIB Ca2+-independent phospholipase A2γ in leukocyte-endothelial cell interactions: An intravital microscopic study in rat mesentery. J Trauma Acute Care Surg. 79:782–789. 2015. View Article : Google Scholar
34	Wang WY, Li J, Yang D, Xu W, Zha RP and Wang YP: OxLDL stimulates lipoprotein-associated phospholipase A2 expression in THP-1 monocytes via PI3K and p38 MAPK pathways. Cardiovasc Res. 85:845–852. 2010. View Article : Google Scholar
35	Zhang KJ, Zhang DL, Jiao XL and Dong C: Effect of phospholipase A2 silencing on acute experimental pancreatitis. Eur Rev Med Pharmacol Sci. 17:3279–3284. 2013.
36	Isenmann R, Rau B and Beger HG: Early severe acute pancreatitis: Characteristics of a new subgroup. Pancreas. 22:274–278. 2001. View Article : Google Scholar
37	Lausevic Z, Lausevic M, Trbojevic-Stankovic J, Krstic S and Stojimirovic B: Predicting multiple organ failure in patients with severe trauma. Can J Surg. 51:97–102. 2008.
38	Schuetz P, Amin DN and Greenwald JL: Role of procalcitonin in managing adult patients with respiratory tract infections. Chest. 141:1063–1073. 2012. View Article : Google Scholar
39	Becker KL, Snider R and Nylen ES: Procalcitonin assay in systemic inflammation, infection, and sepsis: Clinical utility and limitations. Crit Care Med. 36:941–952. 2008. View Article : Google Scholar