ANGIOGENESIS Endothelial Cells Go with the Flow

Endothelial cell (EC) motility plays a critical role in angiogenesis and blood vessel repair. Angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), stimulate EC migration in vitro. Oxidized low density lipoprotein (LDL), which may contribute to the development of atherosclerotic lesions, inhibits EC motility in vitro. Ghosh et al. investigated the mechanisms by which lysophosphatidylcholine (LysoPC), the principle antimigratory agent in oxidized LDL, affects EC motility by treating cultured bovine aortic ECs with lipophilic molecules that affect membrane microviscosity, including -tocopherol, cholesterol, and lysophospholipids. Using fluorescence anisotropy on plasma membrane-enriched cell fractions to measure intramembrane movement of 1,6-diphenyl-1,3,5-hexatriene as an indicator of membrane microviscosity, the authors determined that treatments that caused moderate increases in microviscosity enhanced cell migration, whereas treatments that increased microviscosity beyond a given threshold inhibited migration. Treatment with bFGF and VEGF increased microviscosity to an extent similar to promigratory concentrations of the lipophilic molecules, as determined by fluorescence anisotropy, and decreased the rate of fluorescence recovery after photobleaching a defined membrane region in living cells (another measure of membrane microviscosity). Promigratory concentrations of membrane-active agents and growth factors promoted translocation of Rac, a member of the Rho family of small guanosine triphosphatases implicated in the formation of lamellipodia, into the plasma membrane, whereas LysoPC inhibited Rac translocation. These data indicate that angiogenic growth factors and certain lipophilic molecules can influence cell motility through alterations in membrane microviscosity and the ensuing changes in the localization of key regulatory molecules.

P. K. Ghosh, A. Vasanji, G. Murugesan, S. J. Eppell, L. M. Graham, P. L. Fox, Membrane microviscosity regulates endothelial cell motility. Nature Cell Biol. 4, 894-900 (2002). [Online Journal]