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Understanding aging arteries.

During the last several years, evidence has been accumulating that most vascular disease--arteriosclerosis in particular--is an inflammatory process. In arteriosclerosis--a condition often referred to as "hardening of the arteries" arteries of the cardiovascular system tend to thicken and become stiff, leading to a dramatic increase in one's risk of heart disease, hypertension, and stroke.

Investigators at Indiana University School of Medicine, with support from the Indiana Center for Vascular Biology and Medicine, are exploring these age-related changes in the hope that their findings will lead to a better understanding of arteriosclerosis, as well as preventive strategies and novel treatments for the disease. Neighborhood Heart Watch spoke with Dr. Steven Miller, assistant scientist at the Methodist Research Institute/ Clarian Health who, with colleague Dr. Joseph Unthank, professor of physiology at Indiana University School of Medicine, is researching the underlying mechanisms that may play a key role in the development of vascular disease. The team recently submitted a grant proposal to the National Institute on Aging at the NIH.

NHW: What is the goal of your research?

SM: The long-term goal of our research is to establish the cellular and molecular basis for the aberrant vascular remodeling that occurs in individuals during aging. Once we have identified the mechanisms at work in the disease, we will have novel targets to go after and new pathways of regulation. Basically, we are trying to stop a pathological process that tends to occur with aging. Identifying novel pathways that regulate gene expression during progressive vascular aging will both extend our understanding of age-dependent vascular pathology and promote the development of therapies for the prevention and treatment of age-related cardiovascular disease.

NHW: Are you focusing on one aspect of the process?

SM: We are concentrating on inflammatory molecules, such as cytokines and adhesion molecules, that have been shown to be involved in atherosclerosis and are known to increase with age. We are trying to answer the question, "What is the mechanism that takes place in this process?"

When you have atherosclerosis, you develop plaques, which basically are like bulges that develop in the lining of the vessel. Smooth muscle cells migrate into these areas, where they are not supposed to be. This is the beginning of the development of a plaque which could eventually become large enough to block the artery.

NHW: After the pilot study, did you submit a proposal to the National Institute on Aging for further research?

SM: Yes. The National Institutes of Health issued a program announcement in which they were looking for projects to fund in this area of research. We submitted a proposal for a one-year pilot grant (RO3) to the NIA, where grant applications are reviewed by a peer review committee, which after review assigns a priority score. In this test, the lower the score, the better. Basically, scores range from 100 to 500. Our project received a score of 130.

The other score that you receive is a percentile score, again the lower the better. Our percentile score was 1.4. They contacted us and told us our scores and that our grant had undergone initial peer review. After submitting answers to other administrative issues, we now wait eight weeks. Then they will contact us and tell us whether we will receive funding. I have been told that with our score, funding is likely. In the future, we will use the data from this pilot grant to apply for a longer-term grant (RO1).

Editor Keith March, M.D., Ph.D.

Dr. Keith March is director of the Indiana Center for Vascular Biology and Medicine (ICVBM) at the IU School of Medicine. A goal of the ICVBM is to provide pilot project funding for research efforts undertaken as collaborative engagements between scientists with different areas of expertise. These start-up funds lay the research groundwork that permits scientists such as Drs. Miller and Unthank to garner further grants from the NIH. The above success story is just such a case in which the pilot funding helped new research blossom into a federally recognized program.

For more information about the work of the Center and current research efforts, log onto, contact Dr. Keith March at 317-278-0130, or e-mail:
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Title Annotation:Neighborhood Heart Watch
Author:March, Keith
Publication:Medical Update
Geographic Code:1USA
Date:Apr 1, 2003
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