Session M5.1

Relationship between Local Hemodynamics and Inflammatory Protein Expression in the Mouse Aorta

WR Taylor*, J Oshinski, J Suo, N Willett, M Consolini,
I Campbell, S Nie, DP Giddens

Emory University School of Medicine
Atlanta, GA, USA

It is well established that the local hemodynamic environment within the vasculature is a potent determinant of the localization of atherosclerotic lesions. Numerous cell culture studies have demonstrated that low and/or oscillatory shear stress is associated with the expression of many proteins that are functionally linked to the development of atherosclerosis. However, the ultimate linkage between areas of abnormal shear stress, critical signaling events, inflammatory gene expression and atherosclerosis in vivo is less well established. To more closely examine the relationship between local hemodynamics and expression of proteins known to be involved in the pathogenesis of atherosclerosis, we have employed an approach using a mouse model that is based on establishing correlations between CFD models and localized protein expression using quantum dot antibody conjugates. Quantum dots provide the ability to quantitatively image expression of multiple proteins with a very high degree of spatial localization. Using a combination of micro-CT and small animal MR imaging, we have developed the tools necessary to construct a comprehensive analysis of the local fluid dynamic environment throughout the cardiac cycle. Thus, we can examine expression of selected proteins and compare the patterns of expression directly to the CFD models. Using this approach, we have shown that areas of low and/or oscillatory shear stress correlate with increased expression of ICAM-1 and VCAM-1. Furthermore, under the pathological conditions of an abdominal aortic coarctation (to induce an area of disturbed flow), expression of these same proteins is upregulated in a spatially specific pattern that correlates with the area of newly induced disturbed flow. Similarly, in the setting of early abdominal aortic aneurysm formation, the abnormal flow patterns correlate with increased inflammatory proteins expression. In addition to establishing a novel in vivo approach to studying the relationships between local hemodynamics in mice and endothelial protein expression, these studies demonstrate that dynamic as well as chronic changes in local hemodynamics have a profound effect on inflammatory protein expression in vivo.

(Abstract Control Number: 221)