High-Density Lipoprotein Function in Cardiovascular Disease and Diabetes Mellitus.
High-Density Lipoprotein Function in Cardiovascular Disease and Diabetes Mellitus.
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DOI：
10.1161/atvbaha.117.310222
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Bornfeldt KE
中科院分区：
文献类型：
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作者：
He Y;Kothari V;Bornfeldt KE
他等人的高密度脂蛋白，心血管疾病和糖尿病E11(即，一个小的低胆固醇的高密度脂蛋白颗粒相当于一个大的，富含胆固醇的颗粒)。事实上，临床研究表明，高密度脂蛋白颗粒浓度可能独立于高密度脂蛋白提供有关心血管疾病状态的信息。28，29描述了两种主要的方法来定量人体血浆中的高密度脂蛋白颗粒，一种基于核磁共振30，31，另一种基于离子迁移率分析，32将高密度脂蛋白分为大、中、小三个亚组分。核磁共振方法的一个潜在限制是，它基于对高密度脂蛋白颗粒脂类产生的独特的核磁共振信号的测量，并对高密度脂蛋白脂类的物理性质和高密度脂蛋白体积进行了假设。高密度脂蛋白颗粒浓度是由所有脂蛋白类别(包括极低密度脂蛋白和低密度脂蛋白)的复杂重叠核磁共振信号反卷积得出的，尚未得到正式的生物化学验证。33为了通过离子迁移率分析来量化高密度脂蛋白，高密度脂蛋白颗粒根据它们在载气中的不同迁移率被分离，并使用激光散射直接计数。32，34离子迁移率分析方法使用纳米颗粒和重组高密度脂蛋白进一步校准，得到符合估计的载脂蛋白A-I(载脂蛋白AI)在高密度脂蛋白上的化学计量比的高密度脂蛋白，而不是核磁共振。34大小排除快速蛋白质液相色谱或高效液相色谱系统可用于根据溶液中的颗粒大小分离脂蛋白。此外，高密度脂蛋白颗粒的结构和组成分析(蛋白质组/脂体学方法和免疫亲和层析)提供了对高密度脂蛋白颗粒的额外评估。由于使用不同的方法对高密度脂蛋白进行分类、分离、测量和归一化，以分析高密度脂蛋白功能为中心的研究和实验结果很难进行比较。因此，为了评估作为潜在治疗靶点的高密度脂蛋白功能的问题，未来将需要标准化的可靠、简单和通用的分析方法。
He et al HDL, Cardiovascular Disease, and Diabetes Mellitus e11 (ie, a small cholesterol-poor HDL particle is equivalent to a large, cholesterol-rich particle). Indeed, clinical studies suggest that HDL particle concentration may provide information on CVD status independent of HDL-C. 28, 29 Two principal methods have been described for quantifying HDL particles in human plasma, one based on nuclear magnetic resonance (NMR) 30, 31 and the other based on ion mobility analysis, 32 classifying HDL into large, medium, and small subfractions. One potential limitation of the NMR method is that it is based on measurements of distinctive NMR signals arising from the HDL particle lipids with assumptions made about the physical properties of HDL lipids and HDL volume. The HDL particle concentration is derived from deconvolution of a complex overlapping NMR signal of all lipoprotein classes (including VLDL [very-low-density lipoprotein] and LDL) and has not yet been formally biochemically validated. 33 To quantify HDL by ion mobility analysis, HDL particles are separated on the basis of their differential mobility in a carrier gas and directly counted using laser scattering. 32, 34 The ion mobility analysis method is further calibrated using both nanoparticles and recombinant HDL, yielding molar concentrations of HDL in line with estimated stoichiometry of apoA-I (apolipoprotein AI) on HDL in contrast to NMR. 34 Size exclusion fast protein liquid chromatography or high-performance liquid chromatography systems can then be used separate lipoproteins according to particle size in solution. Furthermore, structure and composition analyses of HDL particles (proteomic/lipidomic methods and immunoaffinity chromatography), provide additional assessment of HDL particles. Because of the use of different methods to classify, isolate, measure, and normalize HDL, it is difficult to compare studies and experimental results centered on analyzing HDL functions. Thus, to assess the issue of HDL function as a potential therapeutic target, standardized robust, simple, and universal analytical methods will be required in the future.