title: Acidosis inhibits endothelial cell apoptosis and function and induces basic fibroblast growth factor and vascular endothelial growth factor expression.
abstract: Endothelial cells are exposed to an acidotic environment in a variety of pathological and physiological conditions. However, the effect of acidosis on endothelial cell function is still largely unknown, and it was evaluated in the present study. Bovine aortic endothelial cells (BAECs) were grown in bicarbonate buffer equilibrated either with 20% CO(2) (pH 7.0, acidosis) or 5% CO(2) (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 acidotic cells than in control cells. Serum deprivation enhanced BAEC apoptosis, and apoptotic cell death was markedly inhibited by acidosis. Additionally, acidosis inhibited FCS-stimulated migration in a modified Boyden chamber assay and FCS-stimulated differentiation into capillary-like structures on reconstituted basement membrane proteins. Conditioned media from BAECs cultured 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 enhanced vascular endothelial growth factor (VEGF) and basic fibroblast growth 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 endothelial cells from apoptosis and inhibits their proangiogenic behavior despite enhanced VEGF and bFGF mRNA expression and bFGF secretion.
authors.affiliation: Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. d.darcangelo@idi.it
authors.forename: D
authors.initials: D
authors.lastname: D'Arcangelo
authors.forename: F
authors.initials: F
authors.lastname: Facchiano
authors.forename: L M
authors.initials: LM
authors.lastname: Barlucchi
authors.forename: G
authors.initials: G
authors.lastname: Melillo
authors.forename: B
authors.initials: B
authors.lastname: Illi
authors.forename: L
authors.initials: L
authors.lastname: Testolin
authors.forename: C
authors.initials: C
authors.lastname: Gaetano
authors.forename: M C
authors.initials: MC
authors.lastname: Capogrossi
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002417:Cattle; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D003470:Culture Media; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D008934:Mitogens; D009687:Nuclear Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2