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. Cardiovascular disease remains the leading cause of death in the United States for the past 50 years. The ability to identify genes that are vital in attenuating and/or preventing cardiovascular damage has yet to be fully elucidated, largely due to the multigenic components of many cardiovascular pathologies. In our proposal, we will investigate the mechanism by which vascular disease, such as atherosclerosis and restenosis can be attenuated and/or completely prevented using a novel delivery method designed in our laboratory. There remains a paucity of information as to the precise mechanisms that are involved in the treatment of vascular disease, which can be essentially broken down into two pathways: 1) acceleration of the endothelial cell barrier; and 2) inhibition of smooth muscle cell proliferation. We have discovered a new envelope coat protein that can be used to efficiently transduce vascular cells in vivo during vascular injury. We will use this novel vector system to over-express therapeutic genes, such as extracellular superoxide dismutase (EC-SOD) and vascular endothelial growth factor (VEGF) to determine whether we can treat vascular disease. In addition, we are in the process of investigating whether we can treat vascular injury in our lean and obese Zucker rat model when we accelerate their diabetic onset using streptozotocin (STZ). We will determine whether growth factor efficacy can be mediated with the co-administration of a ROS scavenging protein, such as EC-SOD. Our microarray analyses using the Affymetrix GeneChip as well as 2-D gel electrophoresis will be used to ascertain other viable candidate mRNAs and proteins, respectively that are altered in vascular and renal damage comparing Zucker diabetic versus normal rat tissues. In all, the studies proposed in this grant will enable us to examine novel techniques to administer genes of interest into the cardiovascular system for the ultimate treatment of diseases, such as vascular injury or renal failure.
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