Email this pageVascular Biology
Redmond Lab
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. Epidemiologic studies from more than 20 countries demonstrate a 20-40% lower cardiovascular disease incidence among alcohol drinkers compared with non-drinkers. Over the last decade, our laboratory has explored the cellular and molecular mechanisms underlying these putative cardiovascular protective effects of alcohol. We investigate the vascular effects of ethanol (i.e., the alcohol found in alcoholic beverages) and of Resveratrol (a red wine polyphenol) using cultured endothelial and smooth muscle cells in vitro in combination with in vivo animal models of vascular remodeling. The laboratory is also interested in how mechanical forces associated with blood flow affect vascular cell biology and function in the context of cardiovascular disease, with particular relevance to atherosclerotic plaque development. We utilize state-of-the-art cellular and molecular techniques to determine signal transduction pathways that are modulated in vascular cells exposed to controlled conditions of shear stress, pressure and stretch. Novel mechanotransduction pathways under investigation in adult vascular cells include Notch and Hedgehog.
Cullen Lab
Dr. John Cullen's research focuses on the effects of 'moderate' and 'binge' patterns of alcohol consumption on the development of atherosclerosis. A biphasic effect of alcohol on the incidence of cardiovascular disease has been documented, where moderate consumption of ethanol exerts a protective effect while chronic alcohol abuse and/or binge drinking are associated with a higher incidence of cardiovascular disorders. It is thus increasingly apparent that in addition to the volume of consumption, the pattern of drinking must be considered. Our research involves investigating the precise cellular mechanisms whereby alcohol elicits these beneficial and/or deleterious effects.
The investigation of the effects of alcohol consumption on two distinct processes, pivotal in the development and destabilization of the atherosclerotic plaque, are underway. Inflammation in the vessel wall is considered to be instrumental in the initiation and progression of atherosclerotic plaques and their destabilization. We are currently investigating the effects of 'moderate' and 'binge' alcohol consumption on monocyte infiltration and the expression of monocyte chemotactic protein-1, and it's receptor CCR2, as well as numerous other inflammatory mediators, in atherosclerotic plaques. Vascular remodeling, mediated in part by proteases and smooth muscle cell apoptosis, plays an important role in many pathophysiological processes including atherosclerosis. Studies are underway to define the effects of 'moderate' and 'binge' alcohol consumption on the expression of matrix metalloproteinases and plasminogen activators, as well as the degree of smooth muscle cell apoptosis, in the unstable atherosclerotic plaque. These studies utilize the genetically modified apolipoprotein E knockout (apo E k/o) mice, which after surgical intervention and a high fat diet, develops an unstable atherosclerotic plaque with many of the key characteristics seen in humans.
We are also undertaking a detailed investigation of the effects of alcohol's primary metabolite, acetaldehyde, which has long been suggested to be involved in a number of alcohols pharmacological and behavioral effects, on vascular cell biology. As well as studying the effects of acetaldhyde on inflammation and vascular remodeling in the apoE k/o flow-cessation/hypocholesteromic model of atherosclerosis, we are also undertaking a detailed analysis of its effects on endothelial cells, smooth muscle cells and monocytes, in vitro.
Given that 65% of the American population consume alcohol, with a 15% binge drinking rate among adults, and that cardiovascular disease remains the leading cause of death in the USA, deciphering the mechanisms mediating alcohols cardiovascular effects will provide significant new information to allow effective interventions to prevent mortality and morbidity associated with cardiovascular disease.