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Cardiotoxicity Study of Tobacco Smoking Using hiPSC-CMs

Institution: Stanford University
Investigator(s): Yingxin Li, Ph.D.
Award Cycle: 2015 (Cycle 24) Grant #: 24FT-0009 Award: $145,800
Subject Area: Early Diagnosis/Pathogenesis
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract

It is well known that tobacco smoking is a major cause of heart and vascular diseases. While the effect of tobacco smoking on the development of hardening of the arteries has been well studied, its role on abnormal rhythms of the heart is less clearly defined. Nicotine is the main constituent of tobacco smoking which is responsible for the elevated risk of the heart and vascular disease and sudden cardiac death. Incidents of adverse cardiac drug reactions are more common in patients with preexisting heart disease than in the general healthy population. The effect of nicotine on heart with cardiac diseases may increase the tobacco-related heart diseases. In addition, the nicotine-associated ion currents disorder might contribute an important role to the mechanism of tobacco smoking-induced abnormal rhythms of the heart. The disparate predispositions of heart cells with variant disease backgrounds to tobacco-induced cardiotoxicities and the mechanisms are less clearly established.

A cellular platform to study the human cardiac toxicity using a library of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from the normal population and patients with various common hereditary cardiac disorders was generated by our lab. Our hypothesis is that nicotine has cardiac toxicities to heart cells and can increase pre-existing arrhythmias in diseased hiPSC-CMs. To test this hypothesis, we will carry out experiments with normal and diseased hiPSC-CMs using assays that were previously developed in our laboratory.

The study will elucidate whether and how tobacco smoking can increase the incidence of the abnormal rhythms of the heart for patients with prior heart diseases. It will also shed light on the mechanism by which nicotine is associated with abnormal rhythms of the heart in patients with preexisting heart diseases. In addition, we anticipate that this project will help improve public health guidelines by further refining the smoking thresholds for cardiotoxicity as well as better identify relevant populations who may be at a higher risk for tobacco-related abnormal rhythms of the heart.