Distinct Proteomic Signatures in 16 HDL (High-Density Lipoprotein) Subspecies
Distinct Proteomic Signatures in 16 HDL (High-Density Lipoprotein) Subspecies
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DOI：
10.1161/atvbaha.118.311607
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发表时间：
2018-12-01
影响因子：
8.7
通讯作者：
Sacks, Frank M.
中科院分区：
文献类型：
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作者：
Furtado, Jeremy D.;Yamamoto, Rain;Sacks, Frank M.
目的 血浆中的 HDL（高密度脂蛋白）是一组异质脂蛋白，通常含有 apo AI 作为主要蛋白质。大多数 HDL 含有来自近 100 种 HDL 相关多肽的额外蛋白质。我们假设其中一些蛋白质定义了独特且稳定的 apo AI HDL 亚种，具有驱动功能和与疾病相关的独特蛋白质组。 方法和结果 我们从 80 名血脂正常的人类参与者（32 名男性，48 名女性；年龄 21-66 岁）中产生了 17 个血浆池。使用免疫亲和分离技术，我们从血浆中分离出含有 apo AI 的物种，然后使用针对 16 种其他 HDL 蛋白成分的抗体来分离组成亚种。我们对先前描述的含有 apo AII、apo CIII 和 apo E 的 HDL 亚种进行了表征；以及 13 个新的 HDL 亚种，通过存在 apo AIV、apo CI、apo CII、apo J、-1-抗胰蛋白酶、-2-巨球蛋白、纤溶酶原、纤维蛋白原、铜蓝蛋白、触珠蛋白、对氧磷酶-1、apo LI 或补体 C3 来定义。新物种的丰度范围为血浆载脂蛋白 AI 总量的 1% 至 18%。 3 至 24 个月内对同一参与者重复采样的组内相关性证明，它们的浓度随着时间的推移保持稳定（0.33-0.86；平均值 0.62）。亚种的一些蛋白质组相对于总 HDL 具有很强的相关性，通常在具有相似功能的亚种之间：脂质代谢、止血、抗氧化或抗炎。排列分析显示16个亚种中有12个亚种的蛋白质组与总HDL的蛋白质组存在显着差异。结论综上所述，相关性和排列分析支持HDL的物种形成。这些新亚种的功能研究及其与疾病关系的确定可能为了解脂蛋白 HDL 系统提供新途径。
Objective HDL (high-density lipoprotein) in plasma is a heterogeneous group of lipoproteins typically containing apo AI as the principal protein. Most HDLs contain additional proteins from a palate of nearly 100 HDL-associated polypeptides. We hypothesized that some of these proteins define distinct and stable apo AI HDL subspecies with unique proteomes that drive function and associations with disease.Approach and Results We produced 17 plasma pools from 80 normolipidemic human participants (32 men, 48 women; aged 21-66 years). Using immunoaffinity isolation techniques, we isolated apo AI containing species from plasma and then used antibodies to 16 additional HDL protein components to isolate compositional subspecies. We characterized previously described HDL subspecies containing apo AII, apo CIII, and apo E; and 13 novel HDL subspecies defined by presence of apo AIV, apo CI, apo CII, apo J, -1-antitrypsin, -2-macroglobulin, plasminogen, fibrinogen, ceruloplasmin, haptoglobin, paraoxonase-1, apo LI, or complement C3. The novel species ranged in abundance from 1% to 18% of total plasma apo AI. Their concentrations were stable over time as demonstrated by intraclass correlations in repeated sampling from the same participants over 3 to 24 months (0.33-0.86; mean 0.62). Some proteomes of the subspecies relative to total HDL were strongly correlated, often among subspecies defined by similar functions: lipid metabolism, hemostasis, antioxidant, or anti-inflammatory. Permutation analysis showed that the proteomes of 12 of the 16 subspecies differed significantly from that of total HDL.Conclusions Taken together, correlation and permutation analyses support speciation of HDL. Functional studies of these novel subspecies and determination of their relation to diseases may provide new avenues to understand the HDL system of lipoproteins.