Technion Rappaport Faculty of Medicine, and Rambam Medical Center, Haifa, Israel.
Curr Opin Lipidol. 2013 Aug;24(4):339-44. doi: 10.1097/MOL.0b013e32835ffcfd.
Improving serum levels of HDL and its subfractions, as well as, oxidative/inflammatory properties has become a fundamental aim in today's atherosclerosis research. Efforts to reach this goal are paralleled by achievements in drug development toward decreasing serum LDL levels and oxidative status.
Paraoxonase1 (PON1) is an HDL-associated enzyme that is deemed responsible for many of the HDL's antiatherogenic and cardioprotective characteristics. PON1 is highly sensitive to variations in its milieu, and endogenous compounds (fatty acids, phospholipids), nutritional ingredients (flavonoids and other antioxidants), and environmental elements (reactive nitrogen and oxygen species, metals, surfactants), significantly affect the enzyme's activities. PON1 was shown to be responsible for some of the HDL antiatherogenic characteristics such as HDL-mediated cholesterol efflux from macrophages, and the inhibition of LDL oxidation.
The present review summarizes the recent literature related to various elements in PON1's milieu that regulate its activities, with an emphasis on its interrelation with components of the human carotid atherosclerotic lesion (plaque) which are in constant contact with circulating HDL-associated PON1.
提高高密度脂蛋白(HDL)及其亚组分的血清水平,以及氧化/炎症特性,已成为当今动脉粥样硬化研究的一个基本目标。为了实现这一目标,人们在开发降低血清 LDL 水平和氧化状态的药物方面取得了进展。
对氧磷酶 1(PON1)是一种与 HDL 相关的酶,被认为是 HDL 许多抗动脉粥样硬化和心脏保护特性的原因。PON1 对其环境的变化非常敏感,内源性化合物(脂肪酸、磷脂)、营养成分(类黄酮和其他抗氧化剂)以及环境元素(活性氮和氧物质、金属、表面活性剂)显著影响酶的活性。PON1 被证明对 HDL 的一些抗动脉粥样硬化特性负责,如 HDL 介导的巨噬细胞胆固醇流出,以及 LDL 氧化的抑制。
本综述总结了最近与调节 PON1 活性的环境中各种因素相关的文献,重点介绍了其与人类颈动脉粥样硬化斑块(斑块)中与循环 HDL 相关的 PON1 不断接触的成分之间的相互关系。