Protein-Defined Subspecies of HDLs (High-Density Lipoproteins) and Differential Risk of Coronary Heart Disease in 4 Prospective Studies.
Protein-Defined Subspecies of HDLs (High-Density Lipoproteins) and Differential Risk of Coronary Heart Disease in 4 Prospective Studies.
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DOI：
10.1161/atvbaha.120.314609
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Jensen MK
中科院分区：
文献类型：
--
作者：
Sacks FM;Liang L;Furtado JD;Cai T;Davidson WS;He Z;McClelland RL;Rimm EB;Jensen MK
HDL 包含定义单个亚种的功能蛋白，每个亚种占总 HDL 的 1% 至 12%。我们研究了 15 个此类亚种与冠心病 (CHD) 的差异关联。我们在四项基于美国的前瞻性研究中测量了 15 种蛋白质定义的 HDL 亚种的血浆载脂蛋白 A1 (apoA1) 浓度。在基线时没有 CVD 的参与者中，有 932 人在 10 至 25 年内患上了 CHD。他们与未经历过 CHD 的对照组进行 1:1 匹配。在每个队列中，通过条件逻辑回归计算每个亚种的风险比（HR），并通过荟萃分析进行合并。与缺乏定义蛋白的 HDL 亚种相比，含有 α-2 巨球蛋白、补体 C3、触珠蛋白或纤溶酶原的 HDL 亚种水平较高，相对风险较高（每增加 1 个 SD，HR 范围分别为 0.96 至 1.11 vs. 0.73 至 0.81；p 异质性 <0.05）。相反，与对应的 HDL 相比，含有 apoC1 或 apoE 的 HDL 的相对风险较低（HR 分别为 0.74，p=0.002 和 0.77，p=0.001）。由参与血栓形成、炎症、免疫和脂质代谢的单一蛋白质定义的几个 HDL 亚种仅占总 HDL 的一小部分，与缺乏该定义蛋白质的 HDL 相比，这些亚种与较高的 CHD 相对风险相关。相比之下，含有 apoC1 或 apoE 的 HDL 与较低的风险密切相关。一个人的 HDL 样本中有益和有害亚种之间的平衡可能决定与 HDL 相关的 CHD 风险和治疗途径。
HDL contains functional proteins that define single subspecies, each comprising 1 to 12% of the total HDL. We studied the differential association with coronary heart disease (CHD) of 15 such subspecies. We measured plasma apolipoprotein A1 (apoA1) concentrations of 15 protein-defined HDL subspecies in four US-based prospective studies. Among participants without CVD at baseline, 932 developed CHD during 10 to 25 years. They were matched 1:1 to controls who did not experience CHD. In each cohort, hazard ratios (HRs) for each subspecies were computed by conditional logistic regression, and combined by meta-analysis. Higher levels of HDL subspecies containing alpha-2 macroglobulin, complement C3, haptoglobin, or plasminogen were associated with higher relative risk compared to the HDL counterpart lacking the defining protein (HR range 0.96 to 1.11 per 1 SD increase vs. 0.73 to 0.81, respectively; p heterogeneity <0.05). In contrast, HDL containing apoC1 or apoE were associated with lower relative risk compared to the counterpart (HR 0.74, p=0.002 and 0.77, p=0.001, respectively). Several subspecies of HDL defined by single proteins that are involved in thrombosis, inflammation, immunity and lipid metabolism are found in small fractions of total HDL and are associated with higher relative risk of CHD compared to HDL that lacks the defining protein. In contrast, HDL containing apoC1 or apoE are robustly associated with lower risk. The balance between beneficial and harmful subspecies in a person’s HDL sample may determine the risk of CHD pertaining to HDL and paths to treatment.
影响因子：
4.5
作者：
Wang L;Sacks FM;Furtado JD;Ricks M;Courville AB;Sumner AE
通讯作者：
Sumner AE