Grant: Project Grant

Cardiac arrhythmias are electrical disturbances that can prevent the heart from working properly. Death resulting from cardiac arrhythmias is one of the leading causes of mortality in most Western societies. Electrical activity in the heart is regulated in part by ion channels. Changes in ion channels can alter cardiac electrical patterns and synchronicity. Sex-related differences in susceptibility to cardiac arrhythmia exist. For instance, men have a higher prevalence of atrial fibrillation (AF) than women. The basis of these sex differences is far from being understood. AF is characterized by very rapid and disorganized electrical impulse. It is the most common arrhythmia in the population and is a significant source of cardiovascular complication and mortality. Currently, the therapeutic options for the treatment of AF have limited effectiveness and adverse effects can often be encountered. In order to develop an improved therapeutic approach for AF, there is a critical need for a detailed understanding of the mechanisms responsible for the higher male susceptibility to this arrhythmia. This information would not only provide valuable insight onto how and why men are more at risk of developing AF than women, but it would also lay foundation for enhanced and sex-specific therapies for the disease. Accordingly, the primary objective of this proposal will be to identify the basic mechanisms responsible for the higher prevalence of AF in men. These studies will be realized using combination of electrophysiological and biochemical techniques while using mouse and human tissues. This work will help to better understand sex-related differences in the pathogenesis of AF. Ultimately, understanding the mechanism responsible for sex differences in cardiac arrhythmias may help to develop improved strategies for the prevention and the management of cardiac arrhythmias in both men and women.