Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process

PLoS One. 2016 Oct 13;11(10):e0164564. doi: 10.1371/journal.pone.0164564. eCollection 2016.

Abstract

Objective: In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age.

Methods: We analyzed four classes of lipoproteins (VLDL, LDL, HDL2, HDL3) from both male (n = 8, 69±4 year-old) and female (n = 25, 53±7 year-old) rheumatoid arthritis (RA) patients as well as controls with similar age (n = 13).

Results: Although RA group showed normal levels of total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and glucose, however, the RA group showed significantly reduced high-density lipoprotein (HDL)-C level and ratio of HDL-C/TC. The RA group showed significantly elevated levels of blood triglyceride (TG), uric acid, and cholesteryl ester transfer protein (CETP) activity. The RA group also showed elevated levels of advanced glycated end (AGE) products in all lipoproteins and severe aggregation of apoA-I in HDL. As CETP activity and TG contents were 2-fold increased in HDL from RA group, paraoxonase activity was reduced upto 20%. Electron microscopy revealed that RA group showed much less HDL2 particle number than control. LDL from the RA group was severely oxidized and glycated with greater fragmentation of apo-B, especially in female group, it was more atherogenic via phagocytosis.

Conclusion: Lipoproteins from the RA patients showed severely altered structure with impaired functionality, which is very similar to that observed in coronary heart patients. These dysfunctional properties in lipoproteins from the RA patients might be associated with high incidence of cardiovascular events in RA patients.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Cell Line
  • Female
  • Humans
  • Lipids / analysis
  • Lipoproteins, HDL / immunology
  • Lipoproteins, HDL / metabolism*
  • Lipoproteins, HDL / ultrastructure*
  • Lipoproteins, HDL2 / immunology
  • Lipoproteins, HDL2 / metabolism*
  • Lipoproteins, HDL2 / ultrastructure*
  • Macrophages / metabolism
  • Macrophages / ultrastructure
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Oxidation-Reduction

Substances

  • Lipids
  • Lipoproteins, HDL
  • Lipoproteins, HDL2
  • glycated lipoproteins, HDL

Grants and funding

This work was supported by a grant from the Mid-carrier Researcher Program (2014-11049455) and Medical Research Center Program (2015R1A5A2009124) through the National Research Foundation (NRF), funded by the Ministry of Science, ICT and Future Planning of Korea. This work also funded by the Ministry of Science, ICT and Future Planning of Korea and a grant from the Ministry of Science, ICT and Future Planning (NRF-2015M3A9B6052011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.