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

University Of Oklahoma Hlth Sciences Ctr, Oklahoma City OK

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Abstract

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.