Summary
The mechanisms of the progression of aortic valve stenosis are unknown. The involvement
of mononuclear cells and of chronic systemic inflammation has been suggested by analysis
of pathological specimens. We hypothesize that shear stress caused by the constricted
aortic orifice contributes to systemic proinflammation by activation of circulating
blood cells and thereby generation of microparticles. Using flow cytometry we analyzed
22 patients with severe aortic valve stenosis (AVS) and 18 patient controls for the
generation of circulating microparticles from platelet-(PMPs: CD31+/CD61+ or CD62P+), leukocyte-(LMPs: CD11b+) and endothelial cell (EMPs: CD62E+) origin. Apart from the constricted valve orifice groups were similar. PMPs were
increased in AVS patients and their number correlated with valvular shear stress.
Monocytes were activated in AVS patients, an observation that was also reflected by
increased numbers of LMPs and by the detection of PMP-monocyte conjugates. Furthermore,
EMPs reflecting the activation of endothelial cells but also conferring systemic inflammatory
activity were increased in AVS patients and correlated with the number of activated
monocytes. In conclusion, we show that AVS is accompanied by increased levels of microparticles
and that shear stress can induce the formation of microparticles. Based on our results
and histologic findings of other investigators the speculation that shear stress related
to aortic valve stenosis induces a vicious circle including the generation of PMPs,
the subsequent activation of monocytes and LMPs and finally the activation of endothelial
cells contributing to the progress of aortic valve stenosis appears to be justified.
Keywords
Microparticles - aortic valve stenosis - endothelial activation