title: Increased levels of circulating microparticles in patients with severe aortic valve stenosis.
abstract: 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.
authors.affiliation: Dept. for Cardiology and Angiology, University Hospital Freiburg, Hugstetterstr. 55, D-79106 Freiburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Diehl
authors.forename: Ferenc
authors.initials: F
authors.lastname: Nagy
authors.forename: Verena
authors.initials: V
authors.lastname: Sossong
authors.forename: Thomas
authors.initials: T
authors.lastname: Helbing
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Manfred
authors.initials: M
authors.lastname: Olschewski
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000209:etiology; D001792:Blood Platelets / Q000502:physiology / Q000648:ultrastructure; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D018056:Hemorheology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D019007:P-Selectin / Q000097:blood; D010316:Particle Size; D015539:Platelet Activation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D019007:P-Selectin