title: Identification and characterization of cells with high angiogenic potential and transitional phenotype in calcific aortic valve.
abstract: Recent data suggest that angiogenesis plays an important role in the pathogenesis of valvular disease. However, the cellular mechanisms underlying this process remain unknown. This study aimed at identifying and characterizing the cellular components responsible for pathological neovascularization in calcific aortic valves (CAV). Immunohistochemical analysis of uncultured CAV tissues revealed that smooth muscle alpha-actin (alpha-SMA)-positive cells, which coexpressed Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2), can be identified prior to the initiation of capillary-like tube formation. In a second step, leaflets of CAV and non-calcific aortic valves (NCAV) were cultured and the cells involved in capillary-like tube formation were isolated. The majority of these cells displayed the same phenotype as non-cultured cells identified in CAV tissues, i.e., expression of alpha-SMA, Tie-2, and VEGFR-2. In comparison to cells isolated from cultures of NCAV leaflets, these cells showed enhanced angiogenic activity as demonstrated by migration and tube assays. The coexpression of VEGFR-2 and Tie-2 together with alpha-SMA suggests both endothelial and mesenchymal properties of the angiogenically activated cells involved in valvular neovascularization. Hence, our findings might provide new insights into the process of pathological angiogenesis in cardiac valves.
authors.affiliation: Department of Cardiovascular Surgery, University Heart Center-Hamburg, Martinistr 52, Hamburg, Germany. chalajou@uke.uni-hamburg.de
authors.forename: Fariba
authors.initials: F
authors.lastname: Chalajour
authors.forename: Hendrik
authors.initials: H
authors.lastname: Treede
authors.forename: Ursula M
authors.initials: UM
authors.lastname: Gehling
authors.forename: Alireza
authors.initials: A
authors.lastname: Ebrahimnejad
authors.forename: Dieter H
authors.initials: DH
authors.lastname: Boehm
authors.forename: Robert K
authors.initials: RK
authors.lastname: Riemer
authors.forename: Suleyman
authors.initials: S
authors.lastname: Ergun
authors.forename: Hermann
authors.initials: H
authors.lastname: Reichenspurner
mesh_terms: D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis; D001021:Aortic Valve / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001681:Biological Assay; D002478:Cells, Cultured; D002633:Chemotaxis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009924:Organ Culture Techniques; D010641:Phenotype; D042787:Receptor, TIE-2 / Q000378:metabolism; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000199:Actins; D015703:Antigens, CD; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2