INSERM U698, University of Paris 7, Paris F-75018 France.
Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1253-62. doi: 10.1161/ATVBAHA.110.203364. Epub 2010 Mar 18.
In addition to its role in the clearance of haptoglobin-hemoglobin (Hp-Hb) complexes, CD163 is a macrophage scavenger receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK). We recently reported that the CD163/TWEAK plasma ratio could be a potential biomarker of atherothrombosis in asymptomatic subjects. In this study, we assessed soluble TWEAK (sTWEAK) and soluble CD163 (sCD163) plasma levels in white males with peripheral artery disease (PAD) and in atherothrombotic femoral plaques to evaluate their relationship with disease. We also analyzed whether Hp-Hb complexes could compete for CD163-mediated TWEAK uptake.
Patients with PAD (n=155) showed a trend toward lower sTWEAK (median [interquartile range]: 134 [110-204] versus 147 [119-205] pg/mL; P=0.067) and higher sCD163 (median [interquartile range]: 367 [269-506] versus 288 [234-369] ng/mL; P<0.001) plasma concentrations than age-matched controls (n=251). sCD163 and sTWEAK plasma levels were negatively correlated in both patients and controls. After stratification according to the severity of disease, sCD163/sTWEAK ratio was significantly increased in patients with more severe disease relative to the other groups (P=0.049). Analysis of conditioned medium obtained from cultured human atherothrombotic femoral plaque samples (n=36) and healthy aortas (n=14) revealed that high amounts of sCD163 were released by the atherothrombotic tissue, whereas sTWEAK presented the opposite trend (P<0.05). Finally, we report a potential association between CD163 shedding and oxidative stress.
Our results suggest that the sCD163/sTWEAK plasma ratio may be associated with atherothrombosis burden in PAD. We hypothesize that an imbalance between TWEAK and CD163 could reflect the progression of atherothrombosis.
除了清除触珠蛋白-血红蛋白（Hp-Hb）复合物的作用外，CD163 还是肿瘤坏死因子样弱凋亡诱导剂（TWEAK）的巨噬细胞清道夫受体。我们最近报道，CD163/TWEAK 血浆比值可能是无症状受试者动脉粥样血栓形成的潜在生物标志物。在这项研究中，我们评估了外周动脉疾病（PAD）患者和动脉粥样血栓性股动脉斑块中的可溶性 TWEAK（sTWEAK）和可溶性 CD163（sCD163）血浆水平，以评估它们与疾病的关系。我们还分析了 Hp-Hb 复合物是否可以竞争 CD163 介导的 TWEAK 摄取。
PAD 患者（n=155）的 sTWEAK（中位数[四分位距]：134[110-204]与 147[119-205]pg/mL；P=0.067）和 sCD163（中位数[四分位距]：367[269-506]与 288[234-369]ng/mL；P<0.001）血浆浓度呈下降趋势与年龄匹配的对照组（n=251）相比。患者和对照组的 sCD163 和 sTWEAK 血浆水平呈负相关。根据疾病严重程度分层后，与其他组相比，疾病更严重的患者 sCD163/sTWEAK 比值显著升高（P=0.049）。对培养的人动脉粥样血栓性股动脉斑块样本（n=36）和健康主动脉（n=14）获得的条件培养基进行分析显示，动脉粥样血栓组织释放大量 sCD163，而 sTWEAK 则呈现相反的趋势（P<0.05）。最后，我们报告了 CD163 脱落与氧化应激之间的潜在关联。
我们的研究结果表明，sCD163/sTWEAK 血浆比值可能与 PAD 中的动脉粥样血栓形成负担有关。我们假设 TWEAK 和 CD163 之间的不平衡可能反映了动脉粥样血栓形成的进展。
