Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia
Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia
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DOI：
10.1161/hc4501.099312
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发表时间：
2001-11-13
期刊：
影响因子：
37.8
通讯作者：
Daniel, WG
中科院分区：
文献类型：
--
作者：
Garlichs, CD;John, S;Daniel, WG
背景--高胆固醇血症是心血管疾病的危险因素，与炎症和高凝状态有关。两者都可以通过CD40系统进行调节。这项研究调查了中度高胆固醇血症患者CD40系统是否上调，以及羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂治疗是否影响CD40系统。方法和结果-15例中度高胆固醇血症患者和15名健康对照受试者。用双标记流式细胞术检测治疗前后血小板CD154、P-选择素和单核细胞CD40的表达。测定血中可溶性CD154和单核细胞趋化蛋白-1(MCP-1)浓度。我们的主要发现如下。中度高胆固醇血症患者血小板表面CD154、P-选择素、单核细胞表面CD40均明显高于正常对照组。患者血浆sCD154水平升高的趋势不明显。单核细胞表面总胆固醇或低密度脂蛋白与CD154呈正相关，与CD40无相关性。后者在体外被C-反应蛋白上调，发现在中度高胆固醇血症患者中显著升高。血小板上的CD154被证明具有生物活性，因为它促进了MCP-1的释放，在体外血小板-内皮细胞共培养模型和患者血清中，MCP-1的释放显著增加。短期应用HMG-CoA还原酶抑制剂可显著下调单核细胞表面CD40和血清MCP-1水平。结论：中度高胆固醇血症患者CD40系统表达上调，这可能是这些患者已知的促炎、促动脉粥样硬化和血栓形成环境的原因之一。
Background-Hypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor.Methods and Results-Fifteen patients with moderate hypercholesterolemia and 15 healthy control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 was analyzed on monocytes before and under therapy with the statin cerivastatin by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. Our main findings were as follows. Patients with moderate hypercholesterolemia showed a significant increase of CD154 and P-selectin on platelets and CD40 on monocytes compared with healthy subjects. Soluble CD154 showed a nonsignificant trend for higher plasma levels in patients. A positive correlation was found for total or LDL cholesterol and CD154, but not for CD40 on monocytes. The latter was upregulated in vitro by C-reactive protein, which was found to be significantly elevated in patients with moderate hypercholesterolemia. CD154 on platelets proved to be biologically active because it enhanced the release of MCP-1, which was markedly elevated in an in vitro platelet-endothelial cell coculture model and in the serum of patients. Short-term therapy with a HMG-CoA reductase inhibitor significantly downregulated CD40 on monocytes and serum levels of MCP-1.Conclusion-Patients with moderate hypercholesterolemia show upregulation of the CD40 system, which may contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.