Nitric oxide induces podokinesis, a scalar micromotion that is transformed into vectorial movement by guidance cues like VEGF, enabling directional endothelial cell migration.
Does nitric oxide mediate VEGF-guided endothelial cell migration?
Directional endothelial cell migration requires both NO-induced podokinesis (scalar motion) and guidance cues like VEGF (vectorial movement), highlighting the critical role of NO in angiogenesis.
Previously, we demonstrated the role of nitric oxide (NO) in transforming epithelial cells from a stationary to locomoting phenotype E. Noiri, T. Peresleni, N. Srivastava, P. Weber, W.F. Bahou, N. Peunova, and M. S. Goligorsky. Am. J. Physiol. 270 (Cell Physiol. 39): C794-C802, 1996 and its permissive function in endothelin-1-stimulated endothelial cell migration (E. Noiri, Y. Hu, W. F. Bahou; C. Keese, I. Giaever, and M. S. Goligorsky, J. Biol: Chem. 272: 1747-1753, 1997). In the present study, the role of functional NO synthase in executing the vascular endothelial growth factor (VEGF)-guided program of endothelial cell migration and angiogenesis was studied in two independent experimental settings. First, VEGF, shown to stimulate NO release from simian virus 40-immortalized microvascular endothelial cells, induced endothelial cell transwell migration, whereas NG-nitro-L-arginine methyl ester (L-NAME) or antisense oligonucleotides to endothelial NO synthase suppressed this effect of VEGF. Second, in a series of experiments on endothelial cell wound healing, the rate of VEGF-stimulated cell migration was significantly blunted by the inhibition of NO synthesis. To gain insight into the possible mode of NO action, we next addressed the possibility that NO modulates cell matrix adhesion by performing impedance analysis of endothelial cell monolayers subjected to NO. The data showed the presence of spontaneous fluctuations of the resistance in ostensibly stationary endothelial cells. Spontaneous oscillations were induced by NO, which also inhibited cell matrix adhesion. This process we propose to term "podokinesis" to emphasize a scalar from of micromotion that, in the presence of guidance cues, e.g., VEGF, is transformed to a vectorial movement. In conclusion, execution of the program for directional endothelial cell migration requires two coexisting messages: NO-induced podokinesis (scalar motion) and guidance cues, e.g., VEGF, which imparts a vectorial component to the movement. Such a requirement for the dual signaling may explain a mismatch in the demand and supply with newly formed vessels in different pathological states accompanied by the inhibition of NO synthase.
Noiri et al. (Thu,) conducted a other in Endothelial cell migration and angiogenesis. VEGF and Nitric Oxide vs. L-NAME or antisense oligonucleotides to endothelial NO synthase was evaluated on Endothelial cell transwell migration and wound healing rate. Nitric oxide induces podokinesis, a scalar micromotion that is transformed into vectorial movement by guidance cues like VEGF, enabling directional endothelial cell migration.