系统性红斑狼疮和类风湿关节炎中的巨噬细胞活化与冠状动脉粥样硬化。
Macrophage activation and coronary atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis.
机构信息
Department of Clinical Pharmacology, School of Medicine, Vanderbilt University, 23rd Avenue South at Pierce Avenue, Nashville, TN 37232-6602, USA.
出版信息
Arthritis Care Res (Hoboken). 2011 Apr;63(4):535-41. doi: 10.1002/acr.20365.
OBJECTIVE
Activation of macrophages may contribute to increased atherosclerosis and coronary artery disease in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Neopterin, a pteridine derivative, is a novel marker of monocyte and macrophage activation that is associated with atherosclerosis and cardiovascular risk in the general population. We examined the hypothesis that macrophage activation is associated with accelerated atherosclerosis in SLE and RA.
METHODS
We compared serum neopterin concentrations, adjusted for age, race, sex, and serum creatinine concentration, in patients with SLE (n=148) or RA (n=166) and control subjects (n=177). In patients with SLE or RA, serum neopterin concentrations were then tested for association (adjusted for age, race, sex, serum creatinine, and medication use) with measures of disease activity or damage, inflammatory markers and mediators, and coronary artery calcium measured by electron beam computed tomography.
RESULTS
Neopterin concentrations were significantly higher in patients with SLE (median 8.0, interquartile range [IQR] 6.5-9.8 nmoles/liter) and RA (median 6.7, IQR 5.3-8.9 nmoles/liter) than controls (median 5.7, IQR 4.8-7.1 nmoles/liter), and were higher in SLE patients than in RA patients (all P<0.001). In SLE, neopterin was significantly correlated with higher erythrocyte sedimentation rate (ESR; P=0.001), tumor necrosis factor α (P<0.001), monocyte chemoattractant protein 1 (P=0.005), and homocysteine concentrations (P=0.01), but in RA, it was only associated with ESR (P=0.01). Neopterin was not associated with coronary calcium in either SLE (P=0.65) or RA (P=0.21).
CONCLUSION
Macrophage activation, reflected by increased serum neopterin concentrations, was increased in both SLE and RA. Neopterin was more robustly associated with atherogenic mediators of inflammation and homocysteine in SLE than in RA, but was not associated with coronary atherosclerosis in either disease.
目的
巨噬细胞的激活可能导致红斑狼疮（SLE）和类风湿关节炎（RA）患者的动脉粥样硬化和冠状动脉疾病增加。新蝶呤是一种新型的单核细胞和巨噬细胞激活标志物，与普通人群的动脉粥样硬化和心血管风险相关。我们检验了这样一个假设，即巨噬细胞的激活与 SLE 和 RA 患者的动脉粥样硬化加速有关。
方法
我们比较了 148 例 SLE 患者、166 例 RA 患者和 177 例对照者的血清新蝶呤浓度，校正年龄、种族、性别和血清肌酐浓度。在 SLE 或 RA 患者中，进一步检测血清新蝶呤浓度与疾病活动或损伤、炎症标志物和介质以及电子束计算机断层扫描测量的冠状动脉钙的相关性（校正年龄、种族、性别、血清肌酐和药物使用情况）。
结果
SLE 患者（中位数 8.0，四分位距 [IQR] 6.5-9.8nmoles/L）和 RA 患者（中位数 6.7，IQR 5.3-8.9nmoles/L）的新蝶呤浓度明显高于对照组（中位数 5.7，IQR 4.8-7.1nmoles/L），且 SLE 患者高于 RA 患者（均 P<0.001）。在 SLE 中，新蝶呤与较高的红细胞沉降率（ESR；P=0.001）、肿瘤坏死因子-α（P<0.001）、单核细胞趋化蛋白 1（P=0.005）和同型半胱氨酸浓度（P=0.01）显著相关，但在 RA 中，仅与 ESR 相关（P=0.01）。新蝶呤与 SLE 患者的冠状动脉钙（P=0.65）或 RA 患者的冠状动脉钙（P=0.21）均无相关性。
结论
反映血清新蝶呤浓度升高的巨噬细胞激活在 SLE 和 RA 中均增加。与 RA 相比，SLE 中，新蝶呤与动脉粥样硬化炎症的致动脉粥样硬化介质和同型半胱氨酸的相关性更强，但在这两种疾病中均与冠状动脉粥样硬化无关。
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