Shear Stress and Endothelial Cell Retention in Critical Lower Limb Ischemia

Abstract

Progressive atherosclerotic stenosis of vessels commonly leads to the development of critical limb and myocardial ischemia. When possible and appropriate, surgical revascularization is attempted, and it is here that we clinically observe the pathological processes of ischemia and reperfusion and their complex effects [1]. Understanding of the role and function of the vascular endothelium has undergone significant changes over the past several decades. In the 1960s Willms-Kretschmer and colleagues referred to altered endothelial cells as being activated and, in doing so, implied a functional consequence to the altered cell morphology [2, 3]. This dynamic view of the endothelium, however, did not ensue into the following decade when, again, it was believed that endothelial cells were nothing more than a passive barrier. It would not be until the 1980s that Pober and colleagues would reexamine the scientific principle and ultimately prove that the vascular endothelium is both dynamic and integral to vascular and systemic equilibrium [4]. The scientific process to better understand the endothelium dates back to the 1800s when von Recklinghausen recognized that vessels were not merely inert tunnels passing through tissue, but living entities lined by cells [5]. The endothelial monolayer comprises the entirety of the vascular system, and it is now recognized that the diversity of these cells is not merely limited by cell type alone, but rather is a function of anatomic hemodynamic variation. The unique interface formed by the endothelium between blood and the surrounding vessel wall allows it to function as a primary mediator in response to shear stress alterations.