Serum lipopolysaccharide neutralizing capacity in ischemic stroke

PLoS One. 2020 Feb 21;15(2):e0228806. doi: 10.1371/journal.pone.0228806. eCollection 2020.

Abstract

Introduction: Periodontitis is associated with increased serum lipopolysaccharide (LPS) activity, which may be one mechanism linking periodontitis with the risk of cardiovascular diseases. As LPS-carrying proteins including lipoproteins modify LPS-activity, we investigated the determinants of serum LPS-neutralizing capacity (LPS-NC) in ischemic stroke. The association of LPS-NC and Aggregatibacter actinomycetemcomitans, a major microbial biomarker in periodontitis, was also investigated.

Materials and methods: The assay to measure LPS-NC was set up by spiking serum samples with E. coli LPS. The LPS-NC, LPS-binding protein (LBP), soluble CD14 (sCD14), lipoprotein profiles, apo(lipoprotein) A-I, apoB, and phospholipid transfer protein (PLTP) activity, were determined in 98 ischemic stroke patients and 100 age- and sex-matched controls. Serum and saliva immune response to A. actinomycetemcomitans, its concentration in saliva, and serotype-distribution were examined.

Results: LPS-NC values ranged between 51-83% in the whole population. Although several of the LPS-NC determinants differed significantly between cases and controls (PLTP, sCD14, apoA-I, HDL-cholesterol), the levels did not (p = 0.056). The main determinants of LPS-NC were i) triglycerides (β = -0.68, p<0.001), and ii) HDL cholesterol (0.260, <0.001), LDL cholesterol (-0.265, <0.001), PLTP (-0.196, 0.011), and IgG against A. actinomycetemcomitans (0.174, 0.011). Saliva A. actinomycetemcomitans concentration was higher [log mean (95% CI), 4.39 (2.35-8.19) vs. 10.7 (5.45-21) genomes/ml, p = 0.023) and serotype D more frequent (4 vs. 0%, p = 0.043) in cases than controls. Serotypeablity or serotypes did not, however, relate to the LPS-NC.

Conclusion: Serum LPS-NC comprised low PLTP-activity, triglyceride and LDL cholesterol concentrations, as well as high HDL cholesterol and IgG against A. actinomycetemcomitans. The present findings let us to conclude that LPS-NC did not associate with stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain Ischemia / complications*
  • Female
  • Humans
  • Lipopolysaccharides / antagonists & inhibitors*
  • Male
  • Stroke / blood*
  • Stroke / complications*

Substances

  • Lipopolysaccharides

Grants and funding

The study was supported by grants from the Academy of Finland (1266053 for PJP), Finnish Dental Society Apollonia, the Paulo foundation, and the Sigrid Juselius foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.