Atrial fibrillation (AF), an age-related cardiac arrhythmia, increases risk of stroke and death. AF can occur in the absence of structural heart disease, but is often associated with CAD, hypertension, and heart failure. Systemic inflammatory markers are elevated in AF patients, and tend to be more elevated in those with persistent than with paroxysmal AF. Inflammatory mechanisms promote atrial remodeling that increases AF persistence and risk of morbidity.
To evaluate AF mechanisms, we study the cellular, biochemical and histologic properties of atrial tissues from surgical patients and from experimental animal models. We study the expression and function of ion channels and other proteins that underlie atrial electrical activity, and evaluate the signaling pathways and genes that are altered in AF. As AF is a highly heritable but complex disease, expression array studies are combined with DNA SNP arrays and DNA/RNA sequencing to assess the impact of genetic variation on mRNA and protein expression. Imaging techniques are used to explore the distribution of inflammatory mediators, inflammatory cells, markers of oxidant stress, and the links to altered atrial architecture. Animal models are used to explore the impact of high rate electrical activity and inflammation.
The combination of approaches will help us to identify and evaluate novel pathways that promote AF and which may be targeted for intervention, in an effort to decrease its incidence and clinical impact.
Atrial fibrillation (AF) is a common age related arrhythmia that can cause shortness of breath, an irregular heart beat, stroke and heart failure. There are approximately 3 million Americans with AF at present, and the number affected is expected to increase to 12-15 million by 2050.
While not immediately life-threatening, AF is a significant medical and economic burden. With the expected rise in AF prevalence due to the aging of the population, efforts to slow the increase in AF are critically important.
Studies in our group are focused on determining the functional pathways by which genetic variations (single nucleotide polymorphisms, SNPs) lead to increased risk of AF. We use state of the art tools and techniques to characterize how AF-related SNPs affect the expression of genes in human atrial tissues and in relevant preclinical studies.
We seek to identify the signaling pathways affected by these genes, in an effort to identify novel targets for pharmacologic intervention that can help to slow the progression of AF and/or decrease its burden.