Angiogenic activation of valvular endothelial cells in aortic valve stenosis
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Angiogenic activation of valvular endothelial cells in aortic valve stenosis. / Chalajour, Fariba; Treede, Hendrik; Ebrahimnejad, Alireza; Lauke, Heidrun; Reichenspurner, Hermann; Ergun, Suleyman.
in: EXP CELL RES, Jahrgang 298, Nr. 2, 15.08.2004, S. 455-64.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Angiogenic activation of valvular endothelial cells in aortic valve stenosis
AU - Chalajour, Fariba
AU - Treede, Hendrik
AU - Ebrahimnejad, Alireza
AU - Lauke, Heidrun
AU - Reichenspurner, Hermann
AU - Ergun, Suleyman
PY - 2004/8/15
Y1 - 2004/8/15
N2 - Here, we demonstrate the angiogenic response of valvular endothelial cells to aortic valve (AV) stenosis using a new ex vivo model of aortic leaflets. Histological analysis revealed neovascularization within the cusps of stenotic but not of non-stenotic aortic valves. Correspondingly, the number of capillary-like outgrowth in 3D collagen gel was significantly higher in stenotic than in non-stenotic valves. Capillary-like sprouting was developed significantly faster in stenotic than in non-stenotic valves. New capillary sprouts from stenotic aortic valves exhibited the endothelial cell markers CD31, CD34 and von-Willebrand factor (vWF) as well as carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), Tie-2 and angiogenesis inhibitor endostatin. Western blot analyses revealed a significant increase of CEACAM1 and endostatin in stenotic aortic valve tissue. Electron microscopic examinations demonstrate that these capillary-like tubes are formed by endothelial cells containing Weibel-Palade bodies. Remarkably, inter-endothelial junctions are established and basement membrane material is partially deposited on the basal side of the endothelial tubes. Our data demonstrate the capillary-like sprout formation from aortic valves and suggest a role of angiogenesis in the pathogenesis of aortic valve stenosis. These data provide new insights into the mechanisms of valvular disorders and open new perspectives for prevention and early treatment of calcified aortic stenosis.
AB - Here, we demonstrate the angiogenic response of valvular endothelial cells to aortic valve (AV) stenosis using a new ex vivo model of aortic leaflets. Histological analysis revealed neovascularization within the cusps of stenotic but not of non-stenotic aortic valves. Correspondingly, the number of capillary-like outgrowth in 3D collagen gel was significantly higher in stenotic than in non-stenotic valves. Capillary-like sprouting was developed significantly faster in stenotic than in non-stenotic valves. New capillary sprouts from stenotic aortic valves exhibited the endothelial cell markers CD31, CD34 and von-Willebrand factor (vWF) as well as carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), Tie-2 and angiogenesis inhibitor endostatin. Western blot analyses revealed a significant increase of CEACAM1 and endostatin in stenotic aortic valve tissue. Electron microscopic examinations demonstrate that these capillary-like tubes are formed by endothelial cells containing Weibel-Palade bodies. Remarkably, inter-endothelial junctions are established and basement membrane material is partially deposited on the basal side of the endothelial tubes. Our data demonstrate the capillary-like sprout formation from aortic valves and suggest a role of angiogenesis in the pathogenesis of aortic valve stenosis. These data provide new insights into the mechanisms of valvular disorders and open new perspectives for prevention and early treatment of calcified aortic stenosis.
KW - Aged
KW - Antigens, CD/metabolism
KW - Antigens, CD34/metabolism
KW - Antigens, Differentiation/metabolism
KW - Aortic Valve/growth & development
KW - Aortic Valve Stenosis/metabolism
KW - Basement Membrane/metabolism
KW - Capillaries/metabolism
KW - Cell Adhesion Molecules
KW - Endostatins/metabolism
KW - Endothelium, Vascular/metabolism
KW - Female
KW - Humans
KW - Intercellular Junctions/metabolism
KW - Male
KW - Microscopy, Electron
KW - Models, Biological
KW - Neovascularization, Pathologic/metabolism
KW - Organ Culture Techniques
KW - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
KW - Receptor, TIE-2/metabolism
KW - Weibel-Palade Bodies/metabolism
KW - von Willebrand Factor/metabolism
U2 - 10.1016/j.yexcr.2004.04.034
DO - 10.1016/j.yexcr.2004.04.034
M3 - SCORING: Journal article
C2 - 15265693
VL - 298
SP - 455
EP - 464
JO - EXP CELL RES
JF - EXP CELL RES
SN - 0014-4827
IS - 2
ER -