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

Abstract

ObjectiveIn order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age.MethodsWe 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).ResultsAlthough 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.ConclusionLipoproteins 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.

Apolipoprotein B binds to enolase-1 and aggravates inflammation in rheumatoid arthritis

“…Structural modification of apoB or apoB-carrying lipoproteins might be an additional regulatory mechanism. For example, LDL from patients with RA is more unstable; it is susceptible to oxidation and already oxidised in patients with RA 15. Indeed, oxLDL, which is enriched in RA, can induce a greater inflammatory response than naïve LDL,15 16 which is supported by our observation of a stronger interaction of oxLDL than native LDL with ENO1 (online supplementary figure 2).…”

Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications

“…Changes to lipid composition in rheumatoid arthritis are not limited to HDL. LDL from rheumatoid arthritis patients had higher levels of glycated end products and was more oxidized than LDL from controls 78. In vitro, LDL from rheumatoid arthritis patients underwent enhanced phagocytosis by macrophages, had higher fatty acid accumulation, and induced approximately threefold greater oxidation.…”

Proteomics Analysis for Verification of Rheumatoid Arthritis Biomarker Candidates Using Multiple Reaction Monitoring

“…HDL cholesterol efflux capacity, that is, the ability to export HDL from immune cells, is damaged in patients with RA. In a previous study, this ability was reported to be related to cardiovascular function . These lipoprotein‐related dysfunctions in patients with RA might be associated with the high incidence of cardiovascular events reported in such patients .…”

“…In a previous study, this ability was reported to be related to cardiovascular function . These lipoprotein‐related dysfunctions in patients with RA might be associated with the high incidence of cardiovascular events reported in such patients . Functional analysis of process networks revealed the differentially expressed proteins to be most strongly associated with blood coagulation, which is activated by coagulation factors that are, in turn, induced by the immune response.…”