THE EFFECTS OF AGES ON CELL BEHAVIOR WITHIN A 3D VASCULAR TISSUE CONSTRUCT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 AGEs对三维血管组织构建中细胞行为的影响 由于国家卫生研究院对试点项目的正式资助延迟，该项目的启动被推迟，工作受到限制。 自从10月初获得试点项目奖的通知以来，我参加了一次咨询委员会会议，以及OUHSC的每月PJI会议。 在11月初的EAC/IAC会议上，我介绍了我过去在3D血管组织模型方面的研究重点，这导致了我的试点项目的发展。 我从委员会那里得到了一些有用的信息，这些信息已经被用来进一步发展我目前的研究项目。 在每月的PJI会议上，每个PJI轮流向小组介绍当前的研究结果，然后进行小组讨论。 唐·卡普拉博士也一直参加每月的PJI会议，担任研究导师。 个人演讲和小组讨论让我了解其他PJIs的研究领域，从而导致更多的互动和未来可能的合作。 试点项目的进展包括修改3D血管组织模型，使其模拟与易发生动脉粥样硬化的血管区域相关的生理条件。 这包括使用人类主动脉内皮细胞和使用IV型胶原蛋白来创建基底膜以支持细胞。 由于这些变化，该系统正在进行表征，并与以前的模型进行比较。 这包括在正常和与动脉粥样硬化相关的炎症条件下对内皮细胞的功能分析。 该项目的其他工作包括高级糖基化终产物（AGE）的形成和表征。 高血糖与糖尿病并发症如动脉粥样硬化的联系机制是晚期糖基化终产物形成的增加。使用牛血清白蛋白和葡萄糖的标准技术用于体外AGE形成。 改良的三维血管组织模型将用于研究AGE对内皮细胞功能和免疫细胞迁移和分化的影响，这些影响将导致动脉粥样硬化斑块形成。 该项目的目标是使用3D血管组织构建来确定与高血糖和动脉粥样硬化相关的潜在机制，以开发新的预防和/或治疗策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Effect of AGEs on Cell Behavior Within a 3D Vascular Tissue Construct This start of this project was delayed and the work has been limited due to the delay of formal funding from NIH for the Pilot Project. Since notification of the Pilot Project award in early October, I have attended an advisory board meeting, as well as monthly PJI meetings at OUHSC. For the EAC/IAC meeting in early November, I presented my research highlights for past work with the 3D vascular tissue model that led to the development of my pilot project. I received some useful information from the committee that has been used to further develop my current research project. For the monthly PJI meetings, each PJI is taking a turn to present current research findings to the group, which is followed by a group discussion. Dr. Don Capra has also been attending the monthly PJI meetings to serve as a research mentor. The individual presentations and the group discussion allows me to understand the research areas of other PJIs that leads to more interaction and possible future collaborations. Progress on the pilot project includes modifications to the 3D vascular tissue model so that it mimics physiological conditions associated with the vascular regions prone to atherosclerosis. This includes using human aortic endothelial cells and using type IV collagen to create a basement membrane to support the cells. Due to these changes, the system is being characterized and compared to the previous model. This includes functional analyses of the endothelial cells under both normal and inflammatory conditions associated with atherosclerosis. Additional work on the project includes the formation and characterization of advanced glycosylation end products (AGE). A proposed mechanism linking hyperglycemia to diabetic complications like atherosclerosis is the increase of advanced glycosylation end products formation. A standard technique using bovine serum albumin and glucose was used for in vitro AGE formation. The modified 3D vascular tissue model will be used to study the effect of AGE on endothelial cell function and immune cell migration and differentiation that would lead to atherosclerotic plaque formation. The goal of this project is to is to use the 3D vascular tissue construct to determine the underlying mechanisms associated with hyperglycemia and atherosclerosis in order to develop new preventative and/or therapeutic strategies.