Identification and characterization of cells with high angiogenic potential and transitional phenotype in calcific aortic valve

• Published in: Experimental cell research Vol. 313; no. 11; pp. 2326 - 2335
• Main Authors: Chalajour, Fariba, Treede, Hendrik, Gehling, Ursula M., Ebrahimnejad, Alireza, Boehm, Dieter H., Riemer, Robert K., Ergun, Suleyman, Reichenspurner, Hermann
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2007; Elsevier BV
• Subjects: Actins - metabolism; Angiogenesis; Antigens, CD - analysis; Aortic Valve - chemistry; Aortic Valve - metabolism; Aortic Valve - pathology; Aortic Valve Stenosis - genetics; Aortic Valve Stenosis - metabolism; Aortic Valve Stenosis - pathology; Biological Assay; Calcific aortic valve; Cardiovascular disease; Cells, Cultured; Cellular biology; Chemotaxis; Endothelial cells; Female; Flow Cytometry; Gene expression; Humans; Male; Molecular biology; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Organ Culture Techniques; Phenotype; Receptor, TIE-2 - metabolism; Smooth muscle cells; Transcription, Genetic; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Angiogenesis; Smooth muscle cells; Endothelial cells; Calcific aortic valve
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2007.02.033

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 α-actin (α-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 α-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 α-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.