Acidosis inhibits endothelial cell apoptosis and function and induces basic fibroblast growth factor and vascular endothelial growth factor expression

Endothelial cells are exposed to an acidotic environment in a variety of pa thological and physiological conditions. However, the effect of acidosis on endothelial cell function is still largely unknown, and it was evaluated i n the present study. Bovine aortic endothelial cells (BAECs) a ere grown in bicarbonate buffer equilibrated either with 20% CO2 (pH 7.0, acidosis) or 5% CO2 (pH 7.4, control). Acidosis inhibited BAEC proliferation in 10% FCS, whereas by day 7 in serum-free medium, cell number was 3-fold higher in ac idotic cells than in control cells. Serum deprivation enhanced BAEC apoptos is, and apoptotic cell death was markedly inhibited by acidosis. Additional ly, acidosis inhibited FCS-stimulated migration in a modified Boyden chambe r assay and FCS-stimulated differentiation into capillary-like structures o n reconstituted basement membrane proteins. Conditioned media from BAECs cu ltured for 48 hours either at pH 7.0 or pH 7.4 enhanced BAEC proliferation and migration at pH 7.4, and both effects were more marked with conditioned medium from BAECs grown in acidotic than in control conditions. Acidosis e nhanced vascular endothelial growth factor (VEGF) and basic fibroblast grow th factor (bFGF) mRNA expression as well as bFGF secretion, and a blocking bFGF antibody inhibited enhanced BAEC migration in response to conditioned medium from acidotic cells. These results show that acidosis protects endot helial cells from apoptosis and inhibits their proangiogenic behavior despi te enhanced VEGF and bFGF mRNA expression and bFGF secretion.