Choi Seungbum, Park Yae Eun, Cheon Eun Jeong, Kim Kyeong Yeon, Kim Miso, Ann Soo Jin, Noh Hye Min, Lee Jaeho, Lee Chan Joo, Lee Seung Taek, Lee Cheolju, Lee Ji Eun, Lee Sang Hak
Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Center for Theragnosis, Biomedical Research Institute, Korean Institute of Science and Technology, Seoul, Korea.
Korean Circ J. 2020 Mar;50(3):236-247. doi: 10.4070/kcj.2019.0195. Epub 2019 Nov 6.
Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.
HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.
After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.
In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.
近期研究已对高密度脂蛋白（HDL）的结构-功能关系进行了探究。本研究旨在识别参与HDL多种生物学功能的HDL相关蛋白并对其进行排序。
对从48名参与者中分离出的HDL进行分析。评估胆固醇流出能力、HDL对一氧化氮生成的影响以及血管细胞黏附分子-1的表达。使用标准化光谱丰度因子比来表示最高四分位数与最低四分位数中已识别蛋白质的相对丰度。
经过多重检验校正后，甲状腺素结合球蛋白、α-1B-糖蛋白、血浆丝氨酸蛋白酶抑制剂、玻连蛋白、血管紧张素原和血清淀粉样蛋白A-4这六种蛋白在胆固醇流出能力最高的HDL中丰度更高（相对丰度比≥2）。相比之下，补体C4-A、α-2-巨球蛋白和免疫球蛋白μ链C区这三种蛋白丰度较低（相对丰度比<0.5）。在一氧化氮生成和血管细胞黏附分子-1表达方面，校正后没有蛋白显示出丰度比≥2或<0.5。与HDL功能参数相关的蛋白属于不同的生物学类别。
总之，本研究对在具有高功能能力的HDL中丰度较高或较低的蛋白进行了排序，并新识别出多种与胆固醇流出能力相关的蛋白。
