GLYCOSYLATION OF APOLIPOPROTEIN C III IN SUBJECTS W/ MYOCARDIAL INFARCTION RISK

小而致密的低密度脂蛋白的存在 颗粒(低密度脂蛋白B亚类)作为血浆中主要的低密度脂蛋白颗粒 一种受遗传因素影响的冠心病危险因素。 低密度脂蛋白B亚类模式的个体(约25%的 人群)的甘油三酯水平相对较高(非常低 密度脂蛋白)极低密度脂蛋白和高密度脂蛋白胆固醇水平降低，a 预测动脉粥样硬化风险增加的个人资料。一个 低密度脂蛋白亚型与心肌梗死风险的后续研究 脑梗塞发现低密度脂蛋白B亚类模式个体有UP 使心肌梗死的风险增加三倍。我们有 先前发现载脂蛋白B(Apo B)是主要的蛋白质 低密度脂蛋白的组成部分，降低了B型低密度脂蛋白的糖基化 与正常(低密度脂蛋白A亚类模式)受试者比较。一种新陈代谢 目前正在进行的研究表明，模式B的受试者表现出 极低密度脂蛋白的分泌显著增加(高达10倍)，极低密度脂蛋白和极低密度脂蛋白 B型受试者的低密度脂蛋白代谢不同于受试者 正常受试者。此外，我们最近发现，极低密度脂蛋白 B型受试者的低密度脂蛋白具有更大的净负表面 电荷密度高于A型受试者的极低密度脂蛋白和低密度脂蛋白。 此外，我们最近发现载脂蛋白C-III，一种次要的 低密度脂蛋白的组成和极低密度脂蛋白高达40%的蛋白质质量 在B模式中，极低密度脂蛋白和低密度脂蛋白的水平大约是 A型极低密度脂蛋白和低密度脂蛋白。载脂蛋白C-III与甘油三酯有关 新陈代谢(它是一种脂肪酶抑制剂)和水平的变化可以解释 B型受试者的甘油三酯水平升高。在……里面 此外，载脂蛋白C-III是一种O-连接的糖蛋白，存在于 血浆有三种形式：双唾液酸化、单唾液化和非糖化 形式。这三种形式的比率的差异可能解释了 B型极低密度脂蛋白和低密度脂蛋白的净负电荷增加 可能会影响C-III与极低密度脂蛋白、低密度脂蛋白和/或 它与脂肪酶的相互作用。根据已知的 载脂蛋白B糖基化在B型低密度脂蛋白、极低密度脂蛋白和低密度脂蛋白代谢中的作用 电荷的差异，看起来很可能实际上会有 B型受试者C-III糖基化的差异。如果 发现这些异构体的比例存在差异，这表明 未来的研究将是必要的，以确定潜在的 这些异构体与极低密度脂蛋白、低密度脂蛋白和 各种脂肪酶。

The presence of small dense low-density lipoprotein (LDL) particles (LDL subclass pattern B) as the major plasma LDL particle is a genetically influenced risk factor for coronary heart disease. Individuals with LDL subclass pattern B (approximately 25% of the population) have relatively increased levels of triglyceride (very low density lipoprotein) VLDL and decreased levels of HDL cholesterol, a profile which would predict an increased risk of atherosclerosis. A subsequent study of LDL sublcass patterns versus risk of myocardial infarction found that individuals with LDL subclass pattern B have up to a threefold increase in riskof myocardial infarction. We have previously found that apolipoprotein B (apo B), the major protein constituent of LDL, has decreased glycosylation in pattern B LDL compared to normal (LDLsubclass pattern A) subjects. A metabolism study currently in progress is showing that pattern B subjects show greatly enhanced (up to 10 fold) secretion of VLDL and that both VLDL and LDL in pattern B subjects are metabolized differently than in normal subjects. In addition, we have recently found that both VLDL and LDL from pattern B subjects possess a greater net negative surface charge density than does VLDL and LDL from pattern A subjects. Further, we havevery recently found that apolipoprotein C-III, a minor component of LDL and up to 40% of the protein mass of VLDL is present in pattern B VLDL and LDL at approximately twice the level present in pattern A VLDL and LDL. Apo C-III is involved in triglyceride metabolism (it is a lipase inhibitor) and altered levels may explain the increased triglyceride levels found in pattern B subjects. In addition, apo C-III is an O-linked glycoprotein which exists in the plasma in three forms: a disialated, monosialated and nonglycosylated form. Differences in the ratios of these three forms may explain the increased net negative charge found in pattern B VLDL and LDL and potentially could influence the binding of C-III with VLDL, LDL and/or its interaction with lipases. Based on the known differences in glycosylation of apoB in pattern B LDL, VLDL and LDL metabolism and the charge differences, it seems likely that there will in fact be differences in the glycosylation of C-III in pattern B subjects. If differences in ratios of these isoforms are found, it would indicate that future studies would be necessary to determine potential differences in interactions of these isoforms with VLDL, LDL and various lipases.