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Tobacco smoke, inflammation & atherosclerosis

Institution: Scripps Research Institute
Investigator(s): William Boisvert, Ph.D. Linda Curtiss, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10RT-0089 Award: $754,932
Subject Area: Cardiovascular Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
It is well known in the scientific community that smoking causes many harmful effects to the blood vessel. One of these effects is called atherosclerosis, a condition in which there is a buildup of materials that causes narrowing of the blood vessel. Advanced atherosclerosis can lead to complete occlusion of a blood vessel when there are other events that trigger blood clots to form in the occluded vessel. These series of events can lead to devastating consequences such as heart attacks and strokes. In recent years, an abundance of scientific evidence suggests that atherosclerosis is strongly influenced by the immune system of the host. When the immune system is not functioning properly due to any number of reasons, atherosclerosis development can be profoundly affected. One of the harmful consequences of smoking is a weakened immune system, as has been documented in the last several decades by numerous scientists. Because atherosclerosis is affected by the immune system and because smoking causes many changes in the immune system, we are asking if one of the ways in which smoking affects atherosclerosis is by causing harmful changes in the immune system that is known to contribute to the development of atherosclerosis. To understand this, we are proposing to use animal models that develop atherosclerosis similar to humans and exposing them to tobacco smoke. This animal model will simulate a human smoker who is in midst of developing atherosclerosis. Because it is virtually impossible to study this phenomenon in humans, animal models such as the ones we are proposing to use are the best alternative. Using these models we can determine in detail the alterations in the immune system brought about by tobacco smoke exposure. We will also find out how atherosclerosis is affected in the animals exposed to smoke compared to unexposed animals. Once we learn the effects of tobacco smoke on the immune system and atherosclerosis, we will attempt to neutralize some of the harmful effects of tobacco smoke by using agents that we think will reverse these effects. If these agents show promise in reversing the deleterious effects of tobacco smoke on atherosclerosis, we will be in a position to possibly develop therapeutic agents that can inhibit the tobacco smoke-mediated development of atherosclerosis.