Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL
Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL
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DOI：
10.1172/jci26206
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发表时间：
2007-03-01
影响因子：
15.9
通讯作者：
Heinecke, Jay W.
中科院分区：
文献类型：
--
作者：
Vaisar, Tomas;Pennathur, Subramaniam;Heinecke, Jay W.
HDL通过促进巨噬细胞泡沫细胞的胆固醇流出降低动脉粥样硬化性心血管疾病的风险。然而，HDL的其他抗动脉粥样硬化特性知之甚少。为了验证脂蛋白携带可能具有新的心脏保护活性的蛋白质的假设，我们使用鸟枪蛋白质组学研究了从健康受试者和冠状动脉疾病（CAD）受试者中分离的HDL的组成。出乎意料的是，我们的分析策略确定了多种补体调节蛋白和多种不同的丝氨酸蛋白酶抑制剂与丝氨酸型内肽酶抑制剂活性。还检测到许多急性期反应蛋白，支持HDL在炎症中具有核心重要性的提议。质谱和生化分析表明，来自CAD受试者的HDL 3选择性富集apoE，提高了HDL在具有临床意义的心血管疾病患者中携带独特蛋白质货物的可能性。总的来说，我们的观察结果表明，HDL在调节补体系统和保护组织免受蛋白水解方面发挥了以前未被怀疑的作用，HDL的蛋白质货物有助于其抗炎和抗动脉粥样硬化特性。
HDL lowers the risk for atherosclerotic cardiovascular disease by promoting cholesterol efflux from macrophage foam cells. However, other antiatherosclerotic properties of HDL are poorly understood. To test the hypothesis that the lipoprotein carries proteins that might have novel cardioprotective activities, we used shotgun proteomics to investigate the composition of HDL isolated from healthy subjects and subjects with coronary artery disease (CAD). Unexpectedly, our analytical strategy identified multiple complement-regulatory proteins and a diverse array of distinct serpins with serine-type endopeptidase inhibitor activity. Many acute-phase response proteins were also detected, supporting the proposal that HDL is of central importance in inflammation. Mass spectrometry and biochemical analyses demonstrated that HDL3 from subjects with CAD was selectively enriched in apoE, raising the possibility that HDL carries a unique cargo of proteins in humans with clinically significant cardiovascular disease. Collectively, our observations suggest that HDL plays previously unsuspected roles in regulating the complement system and protecting tissue from proteolysis and that the protein cargo of HDL contributes to its and inflammatory and antiatherogenic properties.