Abnormal Function of High-Density Lipoprotein Is Associated With Poor Disease Control and an Altered Protein Cargo in Rheumatoid Arthritis
Abnormal Function of High-Density Lipoprotein Is Associated With Poor Disease Control and an Altered Protein Cargo in Rheumatoid Arthritis
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DOI：
10.1002/art.24802
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发表时间：
2009-10-01
影响因子：
--
通讯作者：
Reddy, Srinivasa T.
中科院分区：
文献类型：
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作者：
Charles-Schoeman, Christina;Watanabe, Junji;Reddy, Srinivasa T.
Objective.为了描述类风湿关节炎（RA）患者高密度脂蛋白（HDL）的功能，并确定HDL相关蛋白和酶的特异性差异，以区分促炎HDL和正常HDL。我们研究了132例RA患者。通过无细胞测定评估HDL的促炎功能，并且通过HDL炎症指数>= 1来定义促炎HDL。血浆和HDL相关蛋白载脂蛋白A-I（Apo A-I），结合珠蛋白，血红素结合蛋白，血红蛋白和髓过氧化物酶（MPO）的水平分别通过直接和夹心酶联免疫吸附试验测定。通过市售的测定法测量LCAT：胆固醇酰基转移酶（LCAT）活性。多变量分析显示，年龄、疾病活动度、糜烂性疾病、非高加索人种和吸烟与促炎性RDL显著相关。具有促炎性HDL的患者具有更高的全身炎症指标，并且在RA疾病活动性（使用28个关节的疾病活动性评分）和HDL炎症指数之间观察到显著相关性（r = 0.54，P < 0.0001）。与高密度脂蛋白血症患者相比，高密度脂蛋白血症患者的结合珠蛋白、血红蛋白、载脂蛋白A-I和与高密度脂蛋白相关的髓过氧化物酶水平显著更高（除髓过氧化物酶外，所有比较P < 0.05，P = 0.05）。与健康对照组相比，促炎性HDL患者的LCAT活性最低，但RA患者的HDL水平也显著降低（P = 0.001）。与RA患者和健康对照组中的促炎性HDL相比，RA患者队列中的促炎性HDL与活动性疾病和改变的蛋白质货物相关。高密度脂蛋白的功能与类风湿关节炎患者的全身炎症呈负相关，可能需要进一步研究活动性类风湿关节炎增加心血管发病率和死亡率的机制。
Objective. To characterize the antiinflammatory function of high-density lipoprotein (HDL) in patients with rheumatoid arthritis (RA) and to identify specific differences in HDL-associated proteins and enzymes that distinguish proinflammatory HDL from normal, antiinflammatory HDL.Methods. We studied 132 RA patients. The antiinflammatory function of HDL was assessed by a cell-free assay, and proinflammatory HDL was defined by an HDL inflammatory index >= 1. Plasma and HDL-associated protein levels of apolipoprotein A-I (Apo A-I), haptoglobin, hemopexin, hemoglobin, and myeloperoxidase (MPO) were measured by direct and sandwich enzyme-linked immunosorbent assays, respectively. Lecithin:cholesterol acyltransferase (LCAT) activity was measured by a commercially available assay.Results. Age, disease activity, the presence of erosive disease, non-Caucasian race, and smoking were significantly associated with proinflammatory RDL on multivariate analysis. Patients with proinflammatory HDL had higher measures of systemic inflammation, and a significant correlation was observed between RA disease activity (using the Disease Activity Score in 28 joints) and the HDL inflammatory index (r = 0.54, P < 0.0001). Compared with patients with antiinflammatory HDL, patients with proinflammatory HDL had significantly higher levels of haptoglobin, hemoglobin, Apo A-I, and MPO associated with HDL (P < 0.05 for all comparisons except MPO, which was P = 0.05). LCAT activity was lowest in patients with proinflammatory HDL, but was also significantly reduced in RA patients with antiinflammatory HDL as compared with healthy controls (P = 0.001).Conclusion. Proinflammatory HDL in this RA patient cohort was associated with active disease and an altered protein cargo as compared with antiinflammatory HDL in RA patients and in healthy controls. The antiinflammatory function of HDL was inversely correlated with systemic inflammation in RA patients and may warrant further investigation as a mechanism by which active RA increases cardiovascular morbidity and mortality.