Medicine-Rheumatology, Rm 32-59, UCLA, 1000 Veteran Avenue, Los Angeles, California 90095 USA.
Ann Rheum Dis. 2012 Jul;71(7):1157-62. doi: 10.1136/annrheumdis-2011-200493. Epub 2012 Jan 20.
Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls.
HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL's antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay.
Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2% ± 11.1%) and controls (39.5% ± 8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28>5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=-0.39, p=0.01) and erythrocyte sedimentation rate, (r=-0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL's ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=-0.34, p=0.03).
The cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL's antioxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased cardiovascular (CV) risk.
胆固醇逆向转运（RCT）是高密度脂蛋白（HDL）的主要抗动脉粥样硬化功能。在目前的工作中，作者评估了与健康对照组相比，类风湿关节炎（RA）患者的 HDL 的 RCT 能力是否受损。
从 40 例 RA 患者和 40 名年龄和性别匹配的健康对照者中分离出 HDL。如前所述，进行胆固醇外排、HDL 抗氧化功能和对氧磷酶-1（PON-1）活性的测定。通过商业可得的测定法评估血浆髓过氧化物酶（MPO）活性。
RA 患者（40.2%±11.1%）和对照组（39.5%±8.9%）的 HDL 胆固醇外排能力无显著差异；p=0.75。然而，通过 28 关节计数（DAS28>5.1）测量的高疾病活动度 RA 患者的 HDL 促进胆固醇外排的能力与疾病活动度极低/临床缓解（DAS28<2.6）的患者相比显著降低。胆固醇外排与 DAS28（r=-0.39，p=0.01）和红细胞沉降率之间存在显著相关性（r=-0.41，p=0.0009）。更高的血浆 MPO 活性与 HDL 功能恶化相关（r=0.41，p=0.009（抗氧化能力）；r=0.35，p=0.03（外排））。HDL 促进胆固醇外排的能力与抗氧化功能适度但显著相关（r=-0.34，p=0.03）。
在疾病活动度高的 RA 患者中，HDL 的胆固醇外排能力受损，与全身炎症和 HDL 的抗氧化能力相关。HDL 功能的衰减，独立于 HDL 胆固醇水平，可能表明活跃的 RA 增加心血管（CV）风险的一种机制。
