Med. Klinik mit - SP Nephrologie, Charité - Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
Cardiovasc Res. 2012 Apr 1;94(1):154-62. doi: 10.1093/cvr/cvs089. Epub 2012 Feb 10.
High-density lipoprotein (HDL) is known to have potent anti-inflammatory properties. Monocyte chemoattractant protein-1 is an important pro-inflammatory cytokine in early atherogenesis. There is evidence that HDL can lose its protective function during inflammatory disease. In patients with end-stage renal disease (ESRD), epidemiological studies have documented that the inverse correlation between HDL-cholesterol and cardiovascular risk is lost. Many structural modifications leading to reduced HDL function have been characterized, but the functional consequences are not fully understood.
We showed that HDL from patients with ESRD has a lower anti-inflammatory potential by reduced inhibition of monocyte chemoattractant protein-1 formation in vascular smooth muscle cells. Via a proteomic approach, we identified proteins in HDL from ESRD patients exerting pro-inflammatory actions. By chromatographic separation of proteins and mass-spectrometric analysis, we found serum amyloid A (SAA) to be one molecule acting as a potent pro-inflammatory protein. SAA is enriched in HDL from ESRD patients, correlating with reduced anti-inflammatory capacity. In SAA signal transduction, activation of formyl-peptide receptor 2 is involved. SAA enrichment in HDL of healthy subjects reduced the anti-inflammatory capacity of HDL and correlated with its decreased function.
These results suggest that SAA enrichment of HDL during disease conditions contributes to the decreased protective function. It is a novel finding that SAA acts as a pro-inflammatory molecule to reduce the anti-inflammatory properties of HDL.
高密度脂蛋白（HDL）具有很强的抗炎特性。单核细胞趋化蛋白-1 是动脉粥样硬化早期的一种重要促炎细胞因子。有证据表明，HDL 在炎症性疾病期间可能失去其保护功能。在终末期肾病（ESRD）患者中，流行病学研究已经证明 HDL-胆固醇与心血管风险之间的反比关系消失。已经描述了许多导致 HDL 功能降低的结构修饰，但功能后果尚不完全清楚。
我们表明，ESRD 患者的 HDL 通过减少对血管平滑肌细胞中单核细胞趋化蛋白-1形成的抑制作用，具有较低的抗炎潜力。通过蛋白质组学方法，我们鉴定了 ESRD 患者 HDL 中发挥促炎作用的蛋白质。通过蛋白质的色谱分离和质谱分析，我们发现血清淀粉样蛋白 A（SAA）是一种具有强大促炎作用的分子。SAA 在 ESRD 患者的 HDL 中富集，与抗炎能力降低相关。在 SAA 信号转导中，涉及到形式肽受体 2 的激活。健康受试者 HDL 中的 SAA 富集降低了 HDL 的抗炎能力，并与其功能降低相关。
这些结果表明，疾病状态下 HDL 中 SAA 的富集导致保护功能降低。SAA 作为一种促炎分子来降低 HDL 的抗炎特性是一个新发现。
