The primary goals of the NIH IDeA program to enhance the competitiveness of research institutions and to increase the probability of long-term growth for NIH funding within underfunded states are met by this proposal in several ways. First, networking of scientists within Maine will facilitate collaborations and thereby encourage synergistic effects that occur from exchange of expertise and resources. Second, mentoring of young scientists, an essential part of this proposal, enhances the probability of their success as they compete for NIH funding. Third, each of the three collaborating institutions will purchase equipment and set up methodologies that are currently unavailable in Maine. Thus, each institution will gain a technology that will enable it to be more competitive in future NIH applications. Finally, results of planning meetings, feasibility studies, and preliminary data obtained during this NIH IDeA award will provide the basis for traditional R01 applications. The long term objective of the IDeA program in the state of Maine is to build capacity for translational research (transfer of basic research findings to clinical practice), by creating strong partnerships between basic and clinical researchers. The long term goal of our research program is to identify genes which affect the risk of heart disease. This proposal is focused on the biochemical effects and molecular genetics of ATHS, a gene that may underlie as much as half of the coronary artery disease in the USA. Individuals with the deleterious allele of ATHS (phenotype B) have normal plasma cholesterol levels, but their low density lipoprotein (LDL) is smaller and more dense than normal. In addition, they have slightly elevated LDL and reduced HDL levels and are hypertriglyceridemic. ATHS phenotype B is also associated with insulin resistance and upper body obesity. Because small dense LDL has been shown to be more susceptible to oxidation than normal LDL and that oxidized LDL is thought to play a role in the genesis of atherosclerosis, we plan to test the following hypothesis: Coronary artery bypass graft (CABG) patients with the ATHS phenotype B will have increased oxidative status in plasma and aortic vessel wall tissue compared with CABG patients with the ATHS phenotype A. Because the CABG population is enriched in individuals with phenotype B, it provides an ideal tool to refine the genetic map position of the ATHS gene. We hypothesize that allelic association of tightly linked simple sequence repeat markers with the phenotype B will be observed because of the presence of founder populations residing in the State of Maine.
| Craig, W Y; Rawstron, M W; Rundell, C A et al. (1999) Relationship between lipoprotein- and oxidation-related variables and atheroma lipid composition in subjects undergoing coronary artery bypass graft surgery. Arterioscler Thromb Vasc Biol 19:1512-7 |
