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Cigarette smoke, MCP-1 expression in vivo and atherogenesis

Institution: University of California, Riverside
Investigator(s): Lina Seang Wong, B.S.
Award Cycle: 2002 (Cycle 11) Grant #: 11DT-0244 Award: $50,418
Subject Area: Cardiovascular Disease
Award Type: Dissertation Awards
Abstracts

Initial Award Abstract
Cigarette smoke is a major risk for developing atherosclerosis (“hardening of the arteries”). Atherosclerosis is the build-up of fatty deposits in the walls of arteries that may potentially lead to heart attacks and strokes. Although the connection between cigarette smoking and the development of atherosclerosis is clear, the nature of this link is still unknown. Chemokines, proteins primarily known for their functions in white blood cell trafficking and activation, may be an important clue for linking cigarette smoking to atherosclerosis. For example, it has been shown that chemokines are stimulated by injury (e.g. stress induced by blood flow or chemical injury such as cigarette smoke) to the blood vessel walls and that they attract certain kinds of white blood cells to the injured sites. The attracted cells play an important role in initiating the process of atheroclerosis because when they arrive, they consume large amounts of “bad cholesterol” and change into foam cells that attach to the artery wall and form the initial stage of the disease “plaque” formation. Monocyte chemotactic protein 1 (MCP-1) is one such chemokine that is known to attract the offending cells and therefore can potentially be involved in the generation of smoke-stimulated atheroclerosis.

Recently, our lab has shown that both “first-hand” and “second-hand” cigarette smoke indeed stimulates MCP-1 in cultured human aortic endothelial cells (the kind of cells that form the inner lining of arteries). This important observation shows a strong potential link between cigarette smoke and atherosclerosis in a system using human cells. We now propose to take the next step, which is to test our hypothesis in the more complicated situation of a living animal that inhales smoke as humans do. We propose to determine how cigarette smoke components initiate atherosclerotic plaque formation in a strain of genetically modified mice that are prone to developing these plaques. This will allow us to test for the correlation between cigarette smoke, MCP-1 expression, and their link to atherosclerosis.

The proposed work will benefit the public by providing a better understanding of the cause of atherosclerosis among individuals who are constantly exposed to cigarette smoke, i.e. smokers themselves, waiters and waitress in bars, and spouses and children in households of smokers. Moreover, elucidation of how cigarette smoke components stimulate the expression of MCP-1 may provide the theoretical foundation to devise ways of inhibiting that expression and consequently preventing or ameliorating atherosclerotic plaque formation. Finally, this project may provide additional scientific foundation for TRDRP to properly warn the public, especially those who are at risk for developing atherosclerosis, of the dangers of cigarette smoking.
Publications

effects of first-hand cigarette smoke on structure and function of fibroblasts.
Periodical: Molecular Biology of the Cell Index Medicus:
Authors: Wong LS, Martins-Green M ABS
Yr: 2002 Vol: 13 Nbr: Abs: Pg: 2491

Effects of first- and second-hand smoke on fibroblast proliferation and migration under conditions that mimic human connective tissue.
Periodical: Molecular Biology of the Cell Index Medicus:
Authors: Wong LS, Martins-Green M ART
Yr: 2002 Vol: 13 Nbr: Abs: Pg: 727

Exposure to low levels of mainstream smoke leads to an increase in cell survival.
Periodical: Wound Repair and Regeneration Index Medicus:
Authors: Wong LS, Martins-Green M ABS
Yr: 2003 Vol: 11 Nbr: 2 Abs: A28 Pg:

The effects of first-hand and second-hand smoke on atherosclerotic plaque formation.
Periodical: Wound Repair and Regeneration Index Medicus:
Authors: Wong LS, Martins-Green M ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

The effects of first-hand and second hand smoke on atherosclerotic plaque formation.
Periodical: Molecular Biology of the Cell Index Medicus:
Authors: Wong LS, Yuan H, Martins-Green M ABS
Yr: 2003 Vol: 14 Nbr: Abs: Pg: 2642