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Pathological Angiogenesis and Nicotine:Intracellular Calcium

Institution: Stanford University
Investigator(s): Jieun Lee, Ph.D.
Award Cycle: 2009 (Cycle 18) Grant #: 18FT-0064 Award: $135,000
Subject Area: Cardiovascular Disease
Award Type: Postdoctoral Fellowship Awards
Abstracts

Initial Award Abstract
Cigarette smoking is a major cause of heart disease, tumor and visual loss. Each of these is caused in part by abnormal vessel formation (pathological angiogenesis). We have discovered that tobacco smoke can cause abnormal vessel formation, because of the nicotine within it. Nicotine hijacks the body’s mechanism for growing new blood vessels (the growth of new blood vessels is a normal process required for wound healing). Nicotine does so by activating specific receptors on blood vessels. These receptors (nicotinic acetylcholine receptors, or nAChRs) are normally stimulated by the body’s own molecules, most particularly acetylcholine. Nicotine over-stimulates the nAChRs to cause abnormal vessel growth. Abnormal vessel growth plays a role in the growth of tumors and vessel plaque. Abnormal vessel growth in the back of the eye (age-related maculopathy or AMD) is the major cause of blindness in this country. The major preventable risk factor for tumor, plaque, and AMD is tobacco.

We have shown that certain drugs, which block the nAChR, can reduce abnormal vessel growth in animal models of tumor, plaque, and AMD. Indeed, based upon our work, the FDA has now approved a study in people with AMD to determine if a drug that blocks the nAChR can prevent visual deterioration (by blocking abnormal retinal vessel formation).

However, we still know very little about how the nAChR regulates the cells in blood vessels. This study is directed towards understanding how stimulation of the nAChR activates blood vessels to grow. Our work has already resulted in a possible new drug for a tobacco-related disease. The work that we now propose is intended to provide new and useful knowledge about how the nAChR controls the inner workings of the cells that make up the blood vessel. The study is driven by our intent to refine a new therapeutic strategy for tobacco-related disease.
Publications

The role of nicotine in the pathogenesis of atherosclerosis
Periodical: Atherosclerosis Index Medicus:
Authors: Lee J and Cooke JP ART
Yr: 2011 Vol: 215 Nbr: 2 Abs: Pg: 281-3

Nicotine and pathological angiogenesis
Periodical: Life Sciences_x000D_ Index Medicus:
Authors: Lee J and Cooke JP ART
Yr: 2012 Vol: Nbr: Abs: Pg:

Activation of innate immunity is required for efficient nuclear reprogramming
Periodical: Cell Index Medicus:
Authors: Lee J, Sayed N, Hunter A, Au KF, Wong WH, Mocarski E, Reijo Pera R, Cooke JP ART
Yr: Vol: Nbr: Abs: Pg: