Blood, 15 September 2001, Vol. 98, No. 6, pp. 1644-1644
Endothelial cells: they only look all alike
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.
Zaverio M. Ruggeri
Scripps Research Institute
