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Effects of tobacco and e-cigarettes on heart repair and regeneration

Institution: Childrens Hospital, Los Angeles
Investigator(s): Ching-Ling (Ellen) Lien,
Award Cycle: 2019 (Cycle 30) Grant #: T30IP1028 Award: $678,000
Subject Area: Cardiovascular and Cerebrovascular Disease
Award Type: High Impact Pilot Award

Initial Award Abstract
Myocardial infarction (also called heart attack) is the major cause of heart failure, which continues to be the leading cause of death in the United States and developed countries around the world. The use of tobacco and other tobacco products increases the risk of heart diseases. The fundamental problem leading to heart failure is that human hearts cannot regenerate after heart injury (e.g. heart attack). It is not clear how tobacco smoke affects the capacity of the heart to repair after cardiac injury and increases the chances of developing heart failure. Furthermore, the use of e-cigarettes has gained popularity among young people. E-cigarettes create vapor containing toxic chemicals. The lymphatic vasculature is a specialized network of vessels that drains fluid from tissues and enables immune-cell clearance throughout the body. It has been shown that cardiac lymphatics are essential for heart repair and regeneration after heart injury in a mouse model of myocardial infarction. We propose to test a hypothesis that tobacco can not only increase the chances of a first-time heart attack but can also affect heart repair and regeneration after myocardial infarction by regulating the cardiac lymphatic system. We propose to 1) determine the effects of tobacco and e-cigarettes in zebrafish heart regeneration and cardiac lymphatic vessel functions; 2) determine the effects of tobacco smoke on mouse heart repair, fibrotic scar formation and development of heart failure. Our studies will reveal potential mechanisms on how tobacco and e-cigarettes affect heart repair after myocardial infarction and influence the likelihood in developing heart failure.