Mass Spectrometric Studies of Apolipoprotein Proteoforms and Their Role in Lipid Metabolism and Type 2 Diabetes.
Mass Spectrometric Studies of Apolipoprotein Proteoforms and Their Role in Lipid Metabolism and Type 2 Diabetes.
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DOI：
10.3390/proteomes5040027
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发表时间：
2017-10-15
期刊：
影响因子：
3.3
通讯作者：
Nedelkov D
中科院分区：
文献类型：
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作者：
Nedelkov D
载脂蛋白充当脂蛋白颗粒的结构成分、酶的辅因子和细胞表面受体的配体。大多数载脂蛋白都表现出由单核苷酸多态性 (SNP) 和翻译后修饰（如糖基化、氧化和序列截断）产生的蛋白质形式。这里回顾了最近的研究，将载脂蛋白蛋白质形式与脂质代谢和心脏代谢风险的具体临床指标相关联。针对载脂蛋白 A-I、A-II 和 C-III 的靶向质谱免疫分析应用于大型横断面和纵向临床队列。观察到多种相关性，包括糖尿病和心血管疾病患者的载脂蛋白 A-I 和 A-II 氧化程度较高，以及不同的 apoC-III 蛋白型与血浆甘油三酯相关，表明各个 apoC-III 蛋白型的代谢存在显着差异。这些是此类研究中的首例，将特定的蛋白质形式与临床测量相关联，以确定它们作为疾病诊断、风险分层和治疗决策的潜在临床生物标志物的效用。此类研究为基于 MS 的蛋白质测试的进一步发展和临床转化提供了动力。
Apolipoproteins function as structural components of lipoprotein particles, cofactors for enzymes, and ligands for cell-surface receptors. Most of the apoliporoteins exhibit proteoforms, arising from single nucleotide polymorphisms (SNPs) and post-translational modifications such as glycosylation, oxidation, and sequence truncations. Reviewed here are recent studies correlating apolipoproteins proteoforms with the specific clinical measures of lipid metabolism and cardiometabolic risk. Targeted mass spectrometric immunoassays toward apolipoproteins A-I, A-II, and C-III were applied on large cross-sectional and longitudinal clinical cohorts. Several correlations were observed, including greater apolipoprotein A-I and A-II oxidation in patients with diabetes and cardiovascular disease, and a divergent apoC-III proteoforms association with plasma triglycerides, indicating significant differences in the metabolism of the individual apoC-III proteoforms. These are the first studies of their kind, correlating specific proteoforms with clinical measures in order to determine their utility as potential clinical biomarkers for disease diagnosis, risk stratification, and therapy decisions. Such studies provide the impetus for the further development and clinical translation of MS-based protein tests.