High levels of oxidized fatty acids in HDL are associated with impaired HDL function in patients with active rheumatoid arthritis

Abstract

The objective of this study was to evaluate oxidation products of arachidonic acid and linoleic acid in lipoproteins and synovial fluid (SF) from patients with active rheumatoid arthritis (RA) compared to non-RA controls. High-density lipoproteins (HDL) and low-density lipoproteins (LDL) were isolated from plasma using fast protein liquid chromatography and HDL was isolated from SF using dextran sulfate precipitation. 5-Hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE, 9 hydroxyoctadecadienoic (HODE), and 13-HODE levels were measured in HDL, LDL, and SF by liquid chromatography–tandem mass spectrometry. HDL’s anti-inflammatory function, cholesterol levels, myeloperoxidase (MPO) and paraoxonase 1 (PON1) activities were determined as previously. 5-HETE, 15-HETE, 9-HODE, and 13-HODE levels were significantly increased in HDL and LDL from patients with active RA (n = 10) compared to healthy controls (n = 8) and correlated significantly with measures of systemic inflammation, particularly in HDL (r = 0.65–0.80, p values < 0.004). Higher HETES and HODES in HDL were also significantly correlated with impaired HDL function as measured by the HDL inflammatory index (HII) (r = 0.54–0.58; p values < 0.03). 15-HETE levels and MPO activity were higher in RA SF (n = 10) compared to osteoarthritis (OA) SF(n = 11), and HDL from RA SF had worse function compared to OA SF HDL (HII = 2.1 ± 1.9 and 0.5 ± 0.1), respectively (p < 0.05). Oxidation products of arachidonic acid and linoleic acid are increased in HDL and LDL from patients with active RA compared to healthy controls, and are associated with worse anti- oxidant function of HDL. These results suggest a potential mechanism by which oxidative stress from active RA increases oxidized fatty acids in HDL, promoting HDL dysfunction, and thereby increasing atherosclerotic risk.

High- density lipoprotein function is abnormal in idiopathic inflammatory myopathies

“…In the vascular endothelium, HETEs and HODEs contribute to monocyte and macrophage differentiation (26) as well as to the increased expression of adhesion molecules and release of inflammatory, chemotactic and pro-thrombotic mediators (27). Previous work has linked these lipid mediators to the development of atherosclerosis (6), and work suggests that their accumulation in HDL contributes to HDL dysfunction (5,28).…”

“…Impaired function of HDL has previously been identified in inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and atherosclerosis (4). Oxidized fatty acids including hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs) not only contribute to the oxidation of low density lipoprotein (LDL) but their accumulation in HDL also impairs HDL function, increasing risk of vascular damage (5,6).…”

“…Although it is well established that oxidized lipids and HDL strongly influence the vascular endothelium (4,5), the level and function of these lipoproteins in adult patients with DM and other IIM has not been previously evaluated. In the current work, we investigate HDL function in IIM patients compared to healthy controls, and in a large cohort of IIM patients.…”

Integrated Serum and Fecal Metabolomics Study of Collagen-Induced Arthritis Rats and the Therapeutic Effects of the Zushima Tablet

“…As reported previously (Nakajima et al, 2014 ), reactive oxygen species (ROS) were involved in the pathobiology of RA, and uric acid, the final product of purine and pyrimidine, could get eliminate ROS. Oxidative stress has also been implicated in the pathogenesis of RA (Charles-Schoeman et al, 2017 ). In addition, it was reported that daphnetin in ZT could reduce lipopolysaccharide (LPS)-induced production of ROS, indicating that ZT would exhibit anti-inflammatory effects probably by regulating the level of purine (Shen et al, 2017 ).…”

The Effects of Linoleic Acid Consumption on Lipid Risk Markers for Cardiovascular Disease in Healthy Individuals: A Review of Human Intervention Trials

“…HDL particles help to decrease the risk for CVD through a variety of mechanisms, such as removal of cholesterol from macrophages, improvement of endothelial function, and increasing antioxidant and anti-inflammatory properties [74]. Consumption of a Western diet (high fat, high cholesterol) [75] increased oxidized lipids in HDL, such as oxidized arachidonic acid (AA) and LA [76][77][78]. Oxidized fatty acids in lipoproteins have been suggested to increase atherogenesis [79].…”