In this issue, Morigi and colleagues (page 1828) provide experimental evidence that delineates a pathogenetic mechanism for the postdiarrheal hemolytic uremic syndrome of children. Their findings suggest that the localization of platelet thrombi in the arteriolar circulation and capillaries, as typically seen in the disease, is the consequence of a distinct response of microvascular endothelial cells to verotoxin produced by E coli. These results illustrate 2 concepts that may prove of general significance in our understanding of the causes that trigger arterial thrombosis.
First, the paper provides a well-documented example of the heterogeneity of endothelial cells, based on the variable expression of specific molecules that determine a distinct response to stimuli. Evidence is accumulating that the genetic programming of endothelial cells not only differs in arteries and veins, as well as in larger and smaller vessels, but also defines unique environments in the vascular bed of organs that may explain the preferential localization of disease processes. Thus the same event in different vessels may lead to variable outcomes. Second, the proposed explanation for the effect of verotoxin is a further demonstration of the link between infections and arterial thrombosis. Epidemiologic and experimental studies have called attention to the fact that bacteria and bacterial products may be involved in precipitating acute occlusive incidents on the background of chronic degenerative alterations, such as seen in atherosclerosis.
Morigi and colleagues' results add support to the hypothesis that infections or other stimuli may induce specific changes in gene expression that, for example, could alter the make up of proadhesive molecules in the extracellular matrix and enhance the likelihood of platelet deposition on a ruptured plaque. We have known for some time that endothelial cells are not just a passive barrier to flowing blood. Now we are learning with increasing clarity that their dynamic responses may have a remarkable variety of regional flavors.
