Overexpression of Alternatively Spliced Tissue Factor Induces the Pro-Angiogenic Properties of Murine Cardiomyocytic HL-1 Cells

• Published in: Circulation Journal Vol. 75; no. 5; pp. 1235 - 1242
• Main Authors: Eisenreich, Andreas, Boltzen, Ulrike, Malz, Ronny, Schultheiss, Heinz-Peter, Rauch, Ursula
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2011
• Subjects: Alternative Splicing; Alternatively spliced tissue factor; Angiogenesis; Angiogenesis Inducing Agents; Animals; Cell Line; Cell Movement; Cell Proliferation; Chemokines; Gene Expression; Growth; Mice; Migration; Myocytes, Cardiac - cytology; Myocytes, Cardiac - physiology; Neovascularization, Physiologic; Thromboplastin - genetics
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-10-0783

Background: Tissue factor (TF) is expressed in 2 isoforms: membrane-bound "full length" (fl)TF and soluble alternatively spliced (as)TF. flTF is the major thrombogenic form of TF. Although the function of asTF is poorly understood, it was suggested that asTF contributes to tumor-associated growth and angiogenesis. In the heart of a developing embryo, asTF is expressed much later compared to flTF, but in adult heart, asTF exhibits a distribution pattern similar to that of flTF. Thus, it is possible that asTF may play a role in heart development via pro-angiogenic signaling. The purpose of the present study was to examine the effects of murine asTF overexpression in murine cardiomyocyte-like HL-1 cells on their pro-angiogenic potential, the chemotaxis of monocytic cells, and the expression of fibroblast growth factor-2 (FGF2), cysteine-rich 61 (Cyr61), and vascular endothelial growth factor (VEGF). Methods and Results: Expression of FGF2, Cyr61 and VEGF was assessed on reverse transcription-polymerase chain reaction and western blot. Cell migration, proliferation, and endothelial tube formation assays were carried out. It was found that overexpression of murine asTF in HL-1 cells increases their proliferation and pro-angiogenic properties. The supernatant of murine asTF-overexpressing HL-1 cells induces the chemotaxis of monocytic cells. Conclusions: Overexpression of murine asTF in murine cardiomyocytic cells increases their proliferation, monocyte migration, and pro-angiogenic properties -possibly- mediated by the induction of the pro-migratory and pro-angiogenic factors FGF2, Cyr61 and VEGF. Thus, we propose that murine asTF may serve as a migration- and angiogenesis-promoting factor. (Circ J 2011; 75: 1235-1242)