Gary Owens, PhD
May 21 @ 11:00 am – 12:00 pm
Dichotomous Roles of Inflammation in Atherosclerosis
Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions are the underlying cause of heart attacks [i.e. myocardial infarction (MI)] and stroke which are the leading cause of death in the United States and worldwide. Whereas there is general agreement that atherosclerosis is a chronic inflammatory disease, multiple large clinical trials of drugs that globally inhibit inflammation have failed to get FDA approval due to them having modest or no beneficial effects on the incidence of fatal or non-fatal MI or stroke, and an increase in lethal infection because patients were immuno-compromised. Dr. Owens’s 2026 Berne Lecture will focus on reviewing studies by his lab aimed at identifying novel approaches for reducing the late-stage clinical complications of atherosclerosis by promoting formation of a thick ECM-rich protective fibrous cap. This will include a review of their pioneering studies of genetic, epigenetic, and molecular mechanisms that regulate differentiation and phenotypic transitions of vascular smooth muscle cells (SMC) and endothelial cells (EC) in the pathogenesis of atherosclerosis. In addition, he will describe their studies showing that global inhibition of inflammation with potent broad acting inhibitors of inflammatory cytokines such as IL1b have both detrimental and beneficial effects on late-stage lesion pathogenesis. This includes them demonstrating that IL1R1 signaling in SMC both exacerbates atherosclerosis development but paradoxically also plays a critical beneficial role in promoting formation and maintenance of a protective fibrous cap. These results indicate that there is a need to identify more nuanced inhibitors of inflammation that selectively block detrimental immune responses while maintaining immune responses to pathogens, the key role of inflammation in wound repair (including formation of the fibrous cap), and in inflammation resolution.
Professor of Molecular Physiology and Biological Physics, Professor of Internal Medicine, Division of Cardiology, Robert M. Berne Endowed Professor, Director of the Robert M. Berne Cardiovascular Research Center