Glucosamine, Proteoglycan Synthesis and Atherosclerosis

说明(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。然而，它不受FDA的约束 监管及其长期安全性尚不清楚。氨基葡萄糖用于 蛋白多糖表面糖胺多糖链的合成。血管蛋白多糖 在动脉粥样硬化形成中起关键作用，因为它们滞留了致动脉粥样硬化 动脉壁中的脂蛋白。因此，氨基葡萄糖的使用可能是 会导致动脉粥样硬化。以前的研究在以下方面得出了相互矛盾的结果 氨基葡萄糖的致动脉粥样硬化潜能。一些研究表明， 氨基葡萄糖可能有致动脉粥样硬化的作用，而其他人则建议 抗动脉粥样硬化作用。这项拨款建议调查 血管中的氨基葡萄糖。蛋白多糖的生物合成与脂蛋白滞留 在体外和体内。 这项赠款的主要假设是氨基葡萄糖补充剂将 导致血管平滑肌细胞蛋白多糖合成的改变，这是 会反过来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多糖的性质，氨基葡萄糖的补充 可以增强对动脉粥样硬化的易感性，也可以预防动脉粥样硬化。 这项拨款建议研究补充氨基葡萄糖对机体的影响。 猴主动脉平滑肌合成蛋白多糖的结构与功能 体外培养的肌肉细胞。将进行研究以确定影响 硫酸盐化程度、合成的蛋白多糖的大小和比例 通过血管平滑肌细胞和致动脉粥样硬化脂蛋白的滞留 由这些改变过的蛋白多糖。此外，这笔赠款建议解决 体内补充氨基葡萄糖的效果。低密度脂蛋白受体缺陷小鼠 具有与人类相似的脂蛋白图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 损伤将被确定。拟议研究的结果应该提供 对补充氨基葡萄糖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.