According to the American Heart Association, heart attacks and other forms of cardiovascular disease result in approximately 800,000 deaths annually in the USA, accounting for 36% of the nations total mortality. Population studies from more than 20 countries associate moderate consumption of alcohol with a reduced incidence of cardiovascular disease while, conversely, chronic alcohol abuse is associated with increased mortality. The question of how alcohol causes these effects is important, yet little is known about how it acts mechanistically, particularly in the vasculature. Our vascular biology laboratory focuses on this, and related questions, at a cellular and molecular level.
We investigate vascular effects of alcohol using cultured human cells in vitro in combination with in vivo models of vessel remodeling and atherosclerotic plaque. The confounding role of mechanical forces associated with pulsatile blood flow and its critical effects on vascular cell function in the context of cardiovascular disease is considered, as is the potential contribution of resident vascular stem cells in vessel disease.
Our studies have implicated the Notch signaling pathway in mediating some of alcohol’s vascular cell effects and highlight this pathway as a novel target for ethanol in the body. We are currently investigating how alcohol might differentially control Notch signaling in vascular endothelial and smooth muscle cells, with a focus on γ-secretase proteolytic activity regulation.
Other projects, in collaboration with Prof. Paul A Cahill’s Vascular Biology and Therapeutics Laboratory at Dublin City University, include investigation of the effect of alcohol and its primary metabolite, acetaldehyde, on vascular stem cell self-renewal and differentiation. It is hoped that our studies will yield new information enabling the design of innovative targeted therapies for cardiovascular disease which remains a leading cause of death and disability.