David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.
Clin Rheumatol. 2018 Mar;37(3):615-622. doi: 10.1007/s10067-017-3896-y. Epub 2017 Nov 11.
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.
本研究旨在评估与非类风湿关节炎(RA)对照相比,处于活动期的类风湿关节炎(RA)患者的脂蛋白和滑液(SF)中花生四烯酸和亚油酸的氧化产物。采用快速蛋白液相色谱法从血浆中分离高密度脂蛋白(HDL),采用葡聚糖硫酸盐沉淀法从 SF 中分离 HDL。采用液相色谱-串联质谱法测定 HDL、LDL 和 SF 中 5-羟二十碳四烯酸(HETE)、12-HETE、15-HETE、9 羟基十八碳二烯酸(HODE)和 13-HODE 水平。如前所述,测定 HDL 的抗炎功能、胆固醇水平、髓过氧化物酶(MPO)和对氧磷酶 1(PON1)活性。与健康对照组(n=8)相比,处于活动期的 RA 患者(n=10)的 HDL 和 LDL 中的 5-HETE、15-HETE、9-HODE 和 13-HODE 水平显著升高,且与全身性炎症标志物显著相关,尤其是在 HDL 中(r=0.65-0.80,p 值<0.004)。HDL 中的 HETES 和 HODES 水平升高也与 HDL 炎症指数(HII)(r=0.54-0.58;p 值<0.03)所示的 HDL 功能受损显著相关。与骨关节炎(OA)SF(n=11)相比,RA SF(n=10)中的 15-HETE 水平和 MPO 活性更高,且 RA SF 的 HDL 功能更差(HII=2.1±1.9 和 0.5±0.1)(p<0.05)。与健康对照组相比,处于活动期的 RA 患者的 HDL 和 LDL 中花生四烯酸和亚油酸的氧化产物增加,且与 HDL 的抗氧化功能更差相关。这些结果提示,RA 引起的氧化应激增加了 HDL 中的氧化脂肪酸,导致 HDL 功能障碍,从而增加了动脉粥样硬化的风险。