Abstract:
High-density lipoproteins (HDL) are micelle-like particles consisting of a core of triglycerides and cholesteryl esters surrounded by a shell of phospholipid, cholesterol, and apolipoproteins. HDL is considered \"good\" cholesterol, and its concentration in plasma is used clinically in assessing cardiovascular health. However, these particles vary in structure, composition, and therefore function, and thus can be resolved into subpopulations, some of which have specific cardioprotective properties. Mass measurements of HDL by charge detection mass spectrometry (CD-MS) previously revealed seven distinct subpopulations which could be delineated by mass and charge [Lutomski, C. A. et al. Anal. Chem. 2018]. Here, we investigate the thermal stabilities of these subpopulations; upon heating, the particles within each subpopulation undergo structural rearrangements with distinct transition temperatures. In addition, we find evidence for many new families of structures within each subpopulation; at least 15 subspecies of HDL are resolved. These subspecies vary in size, charge, and thermal stability. While this suggests that these new subspecies have unique molecular compositions, we cannot rule out the possibility that we have found evidence for new structural forms within the known subpopulations. The ability to resolve new subspecies of HDL particles may be important in understanding and delineating the role of unique particles in cardiovascular health and disease.
摘要:
高密度脂蛋白(HDL)是胶束状颗粒,由甘油三酸酯和胆固醇酯的核心组成,被磷脂壳包围,胆固醇,和载脂蛋白。HDL被认为是“好”胆固醇,它在血浆中的浓度在临床上用于评估心血管健康。然而,这些粒子的结构各不相同,composition,因此功能,因此可以分解成亚群,其中一些具有特定的心脏保护特性。通过电荷检测质谱(CD-MS)对HDL进行的质量测量先前揭示了七个不同的亚群,这些亚群可以通过质量和电荷来描绘[Lutomski,C.A.等人。肛交.Chem.2018].这里,我们研究了这些亚群的热稳定性;在加热时,每个亚群中的颗粒经历具有不同转变温度的结构重排。此外,我们在每个亚群中发现了许多新的结构家族的证据;至少有15个HDL亚种得到解决。这些亚种大小不同,charge,和热稳定性。虽然这表明这些新亚种具有独特的分子组成,我们不能排除在已知亚群中发现新结构形式的证据的可能性。解析HDL颗粒的新亚种的能力对于理解和描述独特颗粒在心血管健康和疾病中的作用可能很重要。