David Geffen School of Medicine, 10833 Le Conte Ave., University of California Los Angeles, CA 90095, USA.
Curr Pharm Des. 2011;17(1):17-20. doi: 10.2174/138161211795049787.
Increasing evidence points to the fact that plasma HDL cholesterol levels do not always accurately predict HDL function including reverse cholesterol transport and modulation of inflammation. These functions appear to have evolved as part of our innate immune system. HDL is anti inflammatory in healthy individuals in the absence of systemic oxidative stress and inflammation. In those with chronic illnesses such as renal failure however, HDL may become dysfunctional and actually promote inflammation. HDL may be thought of as a shuttle whose size can be estimated by HDL cholesterol levels. The content of the shuttle however, is what determines the anti inflammatory potential of HDL and can change from one, supporting reverse cholesterol transport to one that is less efficient in carrying out this function. Chronic kidney disease (CKD), and inflammatory disorder, is associated with development of accelerated atherosclerosis and premature death from coronary artery disease (CAD). Patients with CKD present with dyslipidemia, oxidative stress and systemic inflammation. Among the abnormalities in lipid metabolism in these patients is reduced levels and protective capacity of HDL. Recent studies have shown that HDL from patients with end stage renal disease is not capable of preventing LDL oxidation and that it induces monocyte migration in artery wall model systems. Treatment of plasma from these patients, with an HDL mimetic peptide improved the anti inflammatory properties of patient's HDL and made LDL more resistant to oxidative modification. Animal models of kidney disease also had proinflammatory HDL and treatment with the peptide mimetic improved markers of inflammation and anti inflammatory capacity of HDL. Whether HDL mimetic peptides will have therapeutic benefit in patients with renal failure will have to be determined in clinical studies.
越来越多的证据表明，血浆高密度脂蛋白胆固醇水平并不总是能准确预测高密度脂蛋白的功能，包括胆固醇逆向转运和炎症调节。这些功能似乎是作为我们先天免疫系统的一部分进化而来的。在没有全身氧化应激和炎症的健康个体中，HDL 是抗炎的。然而，在患有慢性疾病（如肾衰竭）的个体中，HDL 可能变得功能失调，实际上会促进炎症。HDL 可以被认为是一种载体，其大小可以通过 HDL 胆固醇水平来估计。然而，载体的内容决定了 HDL 的抗炎潜力，并且可以从支持胆固醇逆向转运的一种转变为一种在执行此功能方面效率较低的载体。慢性肾脏病（CKD）和炎症性疾病与动脉粥样硬化加速发展和冠心病（CAD）过早死亡有关。CKD 患者表现出血脂异常、氧化应激和全身炎症。这些患者的脂质代谢异常包括 HDL 水平降低和保护能力降低。最近的研究表明，终末期肾病患者的 HDL 不能防止 LDL 氧化，并且在动脉壁模型系统中诱导单核细胞迁移。用 HDL 模拟肽治疗这些患者的血浆，可改善患者 HDL 的抗炎特性，并使 LDL 更能抵抗氧化修饰。肾病动物模型也具有促炎 HDL，用肽模拟物治疗可改善炎症标志物和 HDL 的抗炎能力。HDL 模拟肽是否会对肾衰竭患者有治疗益处，还需要在临床研究中确定。
