Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression

1 Departments of Surgery, 2 Anatomy and Cell Biology, and 3 Cellular and Integrative Physiology, Indiana University Medical Center, Indianapolis, Indiana 46202 The magnitude of shear stimulus has been shown to determine the level of growth factor expression in cell culture. However, little is known regarding what effect shear level has on specific arterial wall remodeling events in vivo. We have hypothesized that the rate of luminal diameter change and specific remodeling events within the arterial wall layers are dependent on shear level. Selective ligations were made to alter the number of microvascular perfusion units of mesenteric arteries within the same animal to ~50%, 200%, and 400% of control. Arterial blood flow and wall shear rate were correlated with the degree of alteration in perfusion units. Luminal diameters were decreased in 50% arteries by day 2 and increased ~17% and 33%, respectively, in 200% and 400% arteries at day 7 . The rate of diameter change was greatest in 50% and 400% arteries. Wall areas (medial +37%; intimal +18% at day 2 ) and cell densities (intimal +26%; adventitial +44% at day 2 ) were altered only in the 400% arteries. A positive correlation existed by day 2 between endothelial staining for endothelial nitric oxide synthase and shear level. The results demonstrate that shear level influences the rate of luminal expansion, specific remodeling events within each wall layer, and the degree of endothelial gene expression. A greater understanding of how shear level influences specific remodeling events within each wall layer should aid in the development of targeted therapies to manipulate the remodeling process in health and disease. flow-dependent arterial remodeling; shear stress; endothelial nitric oxide synthase; endothelium; smooth muscle; adventitia