UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA.
UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA.
Atherosclerosis. 2024 Oct;397:118565. doi: 10.1016/j.atherosclerosis.2024.118565. Epub 2024 Aug 13.
The structure-function relationships of high-density lipoprotein (HDL) subpopulations are not well understood. Our aim was to examine the interrelationships between HDL particle proteome and HDL functionality in subjects with and without coronary heart disease (CHD).
We isolated 5 different HDL subpopulations based on charge, size, and apolipoprotein A1 (APOA1) content from the plasma of 33 overweight/obese CHD patients and 33 age-and body mass index (BMI)-matched CHD-free subjects. We measured the relative molar concentration of HDL-associated proteins by liquid chromatography tandem mass spectrometry (LC-MS/MS) and assessed particle functionality.
We quantified 110 proteins associated with the 5 APOA1-containing HDL subpopulations. The relative molar concentration of these proteins spanned five orders of magnitude. Only 10 proteins were present in >1% while 73 were present in <0.1% concentration. Only 6 of the 10 most abundant proteins were apolipoproteins. Interestingly, the largest (α-1) and the smallest (preβ-1) HDL particles contained the most diverse proteomes. The protein composition of each HDL subpopulation was altered in CHD cases as compared to controls with the most prominent differences in preβ-1 and α-1 particles. APOA2 concentration was positively correlated with preβ-1 particle functionality (ABCA1-CEC/mg APOA1 in preβ-1) (R = 0.42, p = 0.005), while APOE concentration was inversely correlated with large-HDL particle functionality (SRBI-CEC/mg APOA1 in α-1+α-2) (R = 0.18, p = 0.01).
The protein composition of the different HDL subpopulations was altered differentially in CHD patients. The functionality of the small and large HDL particles correlated with the protein content of APOA2 and APOE, respectively. Our data indicate that distinct particle subspecies and specific particle associated proteins provide new information about the role of HDL in CHD.
高密度脂蛋白（HDL）亚群的结构-功能关系尚不清楚。本研究旨在探讨冠心病（CHD）患者和非冠心病（CHD）患者的 HDL 颗粒蛋白质组与 HDL 功能之间的相互关系。
我们从 33 名超重/肥胖的 CHD 患者和 33 名年龄和体重指数（BMI）匹配的非 CHD 患者的血浆中分离了 5 种不同的基于电荷、大小和载脂蛋白 A1（APOA1）含量的 HDL 亚群。我们通过液相色谱串联质谱（LC-MS/MS）测量了与 HDL 相关的蛋白质的相对摩尔浓度，并评估了颗粒功能。
我们定量了与 5 种 APOA1 含量的 HDL 亚群相关的 110 种蛋白质。这些蛋白质的相对摩尔浓度跨越了五个数量级。只有 10 种蛋白质的浓度超过 1%，而 73 种蛋白质的浓度低于 0.1%。在 10 种最丰富的蛋白质中，只有 6 种是载脂蛋白。有趣的是，最大的（α-1）和最小的（preβ-1）HDL 颗粒含有最多样化的蛋白质组。与对照组相比，CHD 病例中每种 HDL 亚群的蛋白质组成都发生了改变，preβ-1 和α-1 颗粒的变化最为明显。APOA2 浓度与 preβ-1 颗粒功能呈正相关（preβ-1 中 ABCA1-CEC/mg APOA1）（R=0.42，p=0.005），而 APOE 浓度与大 HDL 颗粒功能呈负相关（α-1+α-2 中 SRBI-CEC/mg APOA1）（R=0.18，p=0.01）。
CHD 患者不同 HDL 亚群的蛋白质组成发生了不同的改变。小和大 HDL 颗粒的功能分别与 APOA2 和 APOE 的蛋白含量相关。我们的数据表明，不同的颗粒亚群和特定的颗粒相关蛋白提供了关于 HDL 在 CHD 中的作用的新信息。
