title: Early angiogenic response to shock waves in a three-dimensional model of human microvascular endothelial cell culture (HMEC-1).
abstract: The exact nature of shock wave (SW) action is not, as yet, fully understood, although a possible hypothesis may be that shock waves induce neoangiogenesis. To test this hypothesis, a three-dimensional (3D) culture model on Matrigel was developed employing a human microvascular endothelial cell line (HMEC-1) which was stimulated with low energy soft- focused SW generated by an SW lithotripter. After 12 hours we observed a statistically significant increase in capillary connections subsequent to shock-wave treatment in respect to the control group and a marked 3-hour down-regulation in genes involved in the apoptotic processes (BAX, BCL2LI, GADD45A, PRKCA), in cell cycle (CDKN2C, CEBPB, HK2, IRF1, PRKCA), oncogenes (JUN, WNT1), cell adhesion (ICAM-1), and proteolytic systems (CTSD, KLK2, MMP10). Our preliminary results indicate that microvascular endothelial cells in vitro quickly respond to SW, proliferating and forming vessel-like structures, depending on the energy level employed and the number of shocks released. The early decreased expression in the analysed genes could be interpreted as the first reactive response of the endothelial cells to the external stimuli and the prelude to the events characterizing the neo-angiogenic sequence.
authors.affiliation: Orthopaedic Department, University of Milan, IRCCS Orthopedic Institute Galeazzi, Milan, Italy. valerio.sansone@unimi.it
authors.forename: V
authors.initials: V
authors.lastname: Sansone
authors.forename: M C
authors.initials: MC
authors.lastname: D' Agostino
authors.forename: C
authors.initials: C
authors.lastname: Bonora
authors.forename: F
authors.initials: F
authors.lastname: Sizzano
authors.forename: L
authors.initials: L
authors.lastname: De Girolamo
authors.forename: P
authors.initials: P
authors.lastname: Romeo
mesh_terms: D000161:Acoustic Stimulation; D017209:Apoptosis / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D003094:Collagen; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005786:Gene Expression Regulation; D019220:High-Energy Shock Waves; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D007797:Laminin; D053506:Matrix Metalloproteinase 10 / Q000235:genetics; D009389:Neovascularization, Pathologic; D009687:Nuclear Proteins / Q000235:genetics; D051571:Protein Kinase C-alpha / Q000235:genetics; D011509:Proteoglycans; D051028:bcl-2-Associated X Protein / Q000235:genetics; D000097642:GADD45 Proteins
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D018797:Cell Cycle Proteins; D003094:Collagen; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004338:Drug Combinations; D018799:Intercellular Adhesion Molecule-1; D050856:Interferon Regulatory Factor-1; D007797:Laminin; D053506:Matrix Metalloproteinase 10; D009687:Nuclear Proteins; D051571:Protein Kinase C-alpha; D011509:Proteoglycans; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C493971:CDKN2C protein, human; C545012:CEBPB protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C494257:IRF1 protein, human; C059485:matrigel; C496628:PRKCA protein, human