Glucosamine, Proteoglycan Synthesis and Atherosclerosis

描述（申请人摘要）：氨基葡萄糖是一种营养补充剂 通常用于缓解关节疼痛。但是，它不受FDA 其长期安全性尚不清楚。葡萄糖胺用于 蛋白聚糖上糖胺聚糖链的合成。血管蛋白多糖 在动脉粥样硬化形成中起关键作用， 动脉壁中的脂蛋白因此，葡萄糖胺的使用可能是 致动脉粥样硬化的先前的研究在以下方面产生了相互矛盾的结果： 葡萄糖胺的致动脉粥样硬化潜力。一些研究表明， 葡萄糖胺可能具有促动脉粥样硬化作用，而其他人认为， 抗动脉粥样硬化作用。这项拨款旨在调查以下方面的作用： 血管中的氨基葡萄糖。蛋白聚糖生物合成和脂蛋白滞留 体外和体内。 这项补助金的主要假设是，葡萄糖胺补充剂将 导致血管平滑肌细胞蛋白聚糖合成的改变， 反过来会导致动脉粥样硬化倾向的改变。取决于 这些改变的血管蛋白聚糖、葡萄糖胺补充剂的性质 可以增强对动脉粥样硬化的易感性，或者保护动脉粥样硬化。 这项拨款建议研究葡萄糖胺补充剂对 猴主动脉平滑肌合成蛋白多糖结构与功能 体外培养的肌肉细胞将进行研究以确定 硫酸化程度、大小和合成蛋白聚糖类的比例 血管平滑肌细胞，以及致动脉粥样硬化脂蛋白的滞留 被这些改变的蛋白聚糖所控制此外，这笔赠款还将用于解决 补充葡萄糖胺在体内的作用。LDL受体缺陷小鼠，a 具有类人脂蛋白谱的动脉粥样硬化小鼠模型将 补充口服氨基葡萄糖，动脉粥样硬化的程度 将确定病变。拟议研究的结果应提供 对补充葡萄糖胺的潜在影响的重要见解 动脉粥样硬化性心血管疾病

DESCRIPTION (APPLICANT'S ABSTRACT): Glucosamine is a nutritional supplement commonly used for the relief of joint pain. However, it is not subject to FDA regulation and its long-term safety is unknown. Glucosamine is used in the synthesis of glycosaminoglycan chains on proteoglycans. Vascular proteoglycans play a key role in atherogenesis due to their retention of atherogenic lipoproteins in the arterial wall. Thus, glucosamine use could potentially be atherogenic. Previous studies have yielded conflicting results with respect to the atherogenic potential of glucosamine. Some studies have suggested that glucosamine may have pro=atherogenic effects, while others suggest an anti-atherogenic effect. This grant proposes to investigate the role of glucosamine in vascular . proteoglycan biosynthesis and lipoprotein retention in vitro, andin vivo. The major hypothesis of this grant is that glucosamine supplementation will result in altered proteoglycan synthesis by vascular-smooth muscle cells, which will in turn result in an altered propensity to atherosclerosis. Depending on the nature of these altered vascular proteoglycans, glucosamine supplementation could either enhance susceptibility to, or protect against, atherosclerosis. This grant proposes to study the effect of glucosamine supplementation on the structure and function of proteoglycans synthesized by monkey aortic smooth muscle cells in vitro. Studies will be performed to determine the effect on-degree of sulfation, size, and ratio of classes of proteoglycans synthesized by vascular smooth muscle cells, and the retention of atherogenic lipoproteins by these altered proteoglycans. In addition, this grant proposes to address the effect of glucosamine supplementation in vivo. LDL receptor deficient mice, a mouse model of atherosclerosis that has a human-like lipoprotein profile, will be supplemented with oral glucosamine, and the extent of atherosclerotic lesions will be determined. The findings from the proposed study should provide important insights into the potential effects of glucosamine supplementation on atherosclerotic cardiovascular disease.