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Smoking-induced oxidant stress & platelet integrin alpha....

Institution: The Burnham Institute for Medical Research
Investigator(s): Jeffrey Smith, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10RT-0043 Award: $801,893
Subject Area: Cardiovascular Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
The vasculature consists of the heart, blood vessels, and cells of the blood. The primary function of the vasculature is to deliver nutrients and oxygen to the tissues. This is accomplished by the flow of blood throughout the body. Cigarette smoke (CS) is directly linked to diseases of the vasculature including, heart attack, stroke and atherosclerosis. In fact, the Surgeon Generals report shows that smokers have more than a 70% greater risk for coronary artery disease than do non-smokers. Despite this connection, we still don’t know exactly how CS causes problems in the vasculature.

One recent idea on the role of CS in vascular disease involves oxidant stress. Oxidant stress is a name for a chemical imbalance within the body that involves a specific type of chemical group, called an oxidant. There are many such “oxidants”, and it is widely believed that they are harmful. Over the past decade there has been an increased appreciation for the harmful effects of oxidants on the vasculature. Equally as important, it has become clear that the primary toxins within CS are a group of strong oxidants. Consequently, we believe that smoking causes widespread oxidant stress to the vasculature.

We are most interested in testing the idea that oxidants in CS cause problems with cell adhesion in the vasculature. This laboratory has uncovered evidence that a specific protein on the surface of blood platelets, called Integrin aIIbb3, is susceptible to oxidant stress. Once oxidants have modified aIIbb3, the platelets adhere to the vessel wall, and can block the flow of blood through the vessel. Based on these observations, it is easy to envision how CS could lead to the clogging of arteries (atherosclerosis) and to heart attack. The outcome of our study is likely to shed light into exactly how cigarette smoking harms the vasculature. Our study may also lead to new methods of monitoring the extent of such damage, and new ways of preventing smoking induced coronary artery disease with antioxidants.