Project 452234

Atrial fibrillation (AF) is the most common sustained abnormal heart rhythm (i.e. arrhythmia) worldwide, affecting 1-2% of the population. AF creates a huge socio-economic burden because of increased risk of stroke and the promotion of heart failure. The causes of AF are unclear and complex with the incidence being tightly linked to aging and poor cardiovascular health (i.e., obesity, metabolic syndrome, heart failure, etc.). On the other hand, exercise can strongly reduce AF risk. However, the prevalence of AF in endurance athletes rivals that in heart disease patients. Regardless of the cause of AF, the atria of AF patients show fibrosis, hypertrophy and inflammation. In this grant we will test the role of stretch and TNF, a mechanosensitive cytokine, on adverse atrial changes and AF vulnerability in a mouse model of aortic regurgitation. We will perform our studies on males and females. Our studies provide new insights into the sex-dependent molecular mechanisms and novel therapeutic targets underlying AF.