PMID- 17475245 OWN - NLM STAT- MEDLINE DCOM- 20070817 LR - 20091119 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 313 IP - 11 DP - 2007 Jul 1 TI - Identification and characterization of cells with high angiogenic potential and transitional phenotype in calcific aortic valve. PG - 2326-35 AB - 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. FAU - Chalajour, Fariba AU - Chalajour F AD - Department of Cardiovascular Surgery, University Heart Center-Hamburg, Martinistr 52, Hamburg, Germany. chalajou@uke.uni-hamburg.de FAU - Treede, Hendrik AU - Treede H FAU - Gehling, Ursula M AU - Gehling UM FAU - Ebrahimnejad, Alireza AU - Ebrahimnejad A FAU - Boehm, Dieter H AU - Boehm DH FAU - Riemer, Robert K AU - Riemer RK FAU - Ergun, Suleyman AU - Ergun S FAU - Reichenspurner, Hermann AU - Reichenspurner H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070314 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Actins) RN - 0 (Antigens, CD) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.10.1 (Receptor, TIE-2) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) SB - IM MH - Actins/metabolism MH - Antigens, CD/analysis MH - Aortic Valve/chemistry/metabolism/*pathology MH - Aortic Valve Stenosis/genetics/metabolism/*pathology MH - Biological Assay MH - Cells, Cultured MH - Chemotaxis MH - Female MH - Flow Cytometry MH - Humans MH - Male MH - Neovascularization, Pathologic/genetics/metabolism/*pathology MH - Organ Culture Techniques MH - Phenotype MH - Receptor, TIE-2/metabolism MH - Transcription, Genetic MH - Vascular Endothelial Growth Factor A/pharmacology MH - Vascular Endothelial Growth Factor Receptor-2/metabolism EDAT- 2007/05/04 09:00 MHDA- 2007/08/19 09:00 CRDT- 2007/05/04 09:00 PHST- 2006/08/24 00:00 [received] PHST- 2007/01/03 00:00 [revised] PHST- 2007/02/28 00:00 [accepted] PHST- 2007/05/04 09:00 [pubmed] PHST- 2007/08/19 09:00 [medline] PHST- 2007/05/04 09:00 [entrez] AID - S0014-4827(07)00094-8 [pii] AID - 10.1016/j.yexcr.2007.02.033 [doi] PST - ppublish SO - Exp Cell Res. 2007 Jul 1;313(11):2326-35. doi: 10.1016/j.yexcr.2007.02.033. Epub 2007 Mar 14.