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Titolo:
Oxidized LDL inhibits vascular endothelial growth factor-induced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxide synthase pathway
Autore:
Chavakis, E; Dernbach, E; Hermann, C; Mondorf, UF; Zeiher, AM; Dimmeler, S;
Indirizzi:
Univ Frankfurt, Dept Internal Med 4, Div Mol Cardiol, D-60590 Frankfurt, Germany Univ Frankfurt Frankfurt Germany D-60590 iol, D-60590 Frankfurt, Germany Univ Frankfurt, Dept Internal Med 4, Div Nephrol, D-60590 Frankfurt, Germany Univ Frankfurt Frankfurt Germany D-60590 rol, D-60590 Frankfurt, Germany
Titolo Testata:
CIRCULATION
fascicolo: 16, volume: 103, anno: 2001,
pagine: 2102 - 2107
SICI:
0009-7322(20010424)103:16<2102:OLIVEG>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; PROTEIN-KINASE AKT; ACTIVATION; ANGIOGENESIS; APOPTOSIS; SURVIVAL; PHOSPHORYLATION; ADHESION; LYSOPHOSPHATIDYLCHOLINE; DEPHOSPHORYLATION;
Keywords:
endothelium; lipoproteins; growth substances;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Dimmeler, S Univ Frankfurt, Dept Internal Med 4, Div Mol Cardiol, Theodor Stern Kai 7,D-60590 Frankfurt, Germany Univ Frankfurt Theodor Stern Kai 7 Frankfurt Germany D-60590
Citazione:
E. Chavakis et al., "Oxidized LDL inhibits vascular endothelial growth factor-induced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxide synthase pathway", CIRCULATION, 103(16), 2001, pp. 2102-2107

Abstract

Background-Oxidized LBL (oxLDL) inhibits endothelial cell (EC) migration. Stimulating ECs with vascular endothelial growth factor (VEGF) leads to theactivation of Akt/protein kinase B, which in turn activates endothelial nitric oxide synthase (eNOS) by phosphorylation on serine 1177. VEGF-induced cell migration is dependent on the generation of nitric oxide (NO). Therefore, we investigated whether oxLDL affects EC migration by an inhibitory effect on the Akt/eNOS pathway. Methods and Results-During an in vitro "scratched wound assay," oxLDL, dose-dependently inhibited the VEGF-induced migration of human umbilical vein endothelial cells, Western blot analysis revealed that oxLDL dose- and time-dependently led to dephosphorylation and thus deactivation of Akt. Moreover, oxLDL inhibited the VEGF-induced generation of NO, as detected and quantified using a fluorescent NO indicator, 4,5-diaminofluorescein diacetate. Overexpression of a constitutively active Akt construct (Akt T308D/S473D) ora phosphomimetic eNOS construct (eNOS S1177D) almost completely reversed the inhibitory effect of oxLDL on VEGF-induced EC migration and NO generation. Conclusions-Our data indicate that oxLDL-induced dephosphorylation of Akt,followed by impaired eNOS activation: reduces the intracellular level of NO and thereby inhibits VEGF-induced EC migration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 02:19:48