Title

The Effects of Nicotine on Stem Cell Derived Cardiomyocytes

Publication Date

2018-07-03

Availability

Embargoed

Embargo Period

2019-07-03

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biomedical Engineering (Engineering)

Date of Defense

2018-06-22

First Committee Member

Herman Cheung

Second Committee Member

Daniel Pelaez

Third Committee Member

C.Y Charles Huang

Fourth Committee Member

Edward Dauer

Fifth Committee Member

Wayne Balkan

Abstract

Smoking continues to be the number one cause of preventable death in the United States and 1 in 10 cardiovascular disease deaths is related to smoking. In addition to tobacco usage many users attempt to curb nicotine withdrawal symptoms while quitting tobacco through the use of nicotine replacement therapies such as gums, transdermal passages and as of recently, electronic cigarettes. Persistent nicotine usage, however, still presents a risk factor for the development of cardiovascular disease. Despite this the molecular mechanism that underlie the development of nicotine induced cardiovascular disease remain unclear. Therefore, the effect of nicotine on cardiomyocytes is of great interest to the scientific community. I evaluate two potential models of cardiomyocytes for investigation into the effects of nicotine on cardiomyocytes. Using an induced pluripotent stem cell model of cardiomyocytes, I investigate changes in induced pluripotent stem cell derived cardiomyocytes subject to nicotine addition at every media change. In these studies, I show that nicotine induces increased intracellular Ca2+ loads through activation of a7 nicotinic acetylcholine receptors. I show that nicotine induced increased Ca2+ load leads to increased levels of kinase activity. Finally, I show that cardiomyocytes subject to nicotine treatment display a fetal like gene program that is indicative of hypertrophic growth, commonly associated with cardiovascular disease.

Keywords

nicotine; cardiomyocytes; induced pluripotent stem cells; dental stem cells

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