Effects of dysfunctional HDL on coronary artery disease

高密度脂蛋白胆固醇(HDLC)是冠心病的负性危险因素。高密度脂蛋白具有多种抗动脉粥样硬化的功能，包括抗炎和抗氧化，以及促进胆固醇的反向运输。然而，据报道，在炎症、糖尿病和氧化应激等条件下，高密度脂蛋白可能会失去其抗动脉粥样硬化的特性，而变得有利于动脉粥样硬化(功能障碍)。在这项研究中，我们评估了日本患者的高密度脂蛋白功能，并研究了功能障碍的高密度脂蛋白对冠状动脉疾病(CAD)的影响。1)颗粒白细胞衍生的髓过氧化物酶(MPO)促进脂蛋白的氧化，而对氧磷酶1(PON1)对高密度脂蛋白(HDL)具有抗氧化特性。我们发现血清MPO/PON1比值反映了高密度脂蛋白的抗炎特性。此外，MPO/PON1比率与日本患者冠状动脉病变的发生率显著相关。2)匹伐他汀具有升高血浆高密度脂蛋白胆固醇水平和降低低密度脂蛋白胆固醇水平的作用。我们证明了匹伐他汀还可以增强高密度脂蛋白的胆固醇外流能力和抗氧化性能。

High-density lipoprotein cholesterol (HDL-C) is a negative risk factor for CAD. HDL exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become pro-atherogenic (dysfunctional) under conditions such as inflammation, diabetes, and oxidative stress. In this study, we evaluated HDL function in Japanese patients, and investigated effects of dysfunctional HDL on coronary artery disease (CAD).1) Granular leukocyte-derived myeloperoxidase (MPO) promotes oxidation of lipoproteins, while paraoxonase 1 (PON1) has antioxidant properties for high-density lipoprotein (HDL). We found that serum MPO/PON1 ratio reflect anti-inflammatory properties of HDL. Furthermore, MPO/PON1 ratio was significantly associated with the prevalence of coronary lesions in Japanese patients.2) Pitavastatin has a function of increasing plasma HDL-C levels as well as decreasing low-density lipoprotein cholesterol levels. We demonstrated that pitavastatin also enhances cholesterol efflux capacity and antioxidative properties of HDL.