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Titolo:
Transcriptional control of deformation-induced preproendothelin-1 gene expression in endothelial cells
Autore:
Lauth, M; Wagner, AH; Cattaruzza, M; Orzechowski, HD; Paul, M; Hecker, M;
Indirizzi:
Univ Gottingen, Dept Cardiovasc Physiol, D-37073 Gottingen, Germany Univ Gottingen Gottingen Germany D-37073 iol, D-37073 Gottingen, Germany Free Univ Berlin, Inst Clin Pharmacol & Toxicol, D-1000 Berlin, Germany Free Univ Berlin Berlin Germany D-1000 & Toxicol, D-1000 Berlin, Germany
Titolo Testata:
JOURNAL OF MOLECULAR MEDICINE-JMM
fascicolo: 8, volume: 78, anno: 2000,
pagine: 441 - 450
SICI:
0946-2716(2000)78:8<441:TCODPG>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; SMOOTH-MUSCLE CELLS; NUCLEOTIDE-SEQUENCE; SAPHENOUS-VEIN; ORGAN-CULTURE; DISEASE; RAT; PRESSURE; STRETCH; GATA-2;
Keywords:
blood pressure; endothelin-1; decoy oligodeoxynucleotide; activator protein-1; restenosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Hecker, M Univ Gottingen, Dept Cardiovasc Physiol, Humboldtallee 23, D-37073 Gottingen, Germany Univ Gottingen Humboldtallee 23 Gottingen Germany D-37073 rmany
Citazione:
M. Lauth et al., "Transcriptional control of deformation-induced preproendothelin-1 gene expression in endothelial cells", J MOL MED-J, 78(8), 2000, pp. 441-450

Abstract

Deformation-induced synthesis of endothelin-1 (ET-1) in endothelial cells exposed to high blood pressure may play an important role in vein graft disease and in restenosis following percutaneous transluminal angioplasty. Effective inhibitors of preproendothelin ET-1 (ppET-1) processing to ET-1 are not available, and blockade of ppET-1 expression may therefore emerge as analternative therapeutic approach. To evaluate this, we investigated deformation-sensitive transcription factors controlling ppET-1 expression in bothnative (rabbit carotid artery and jugular vein) and cultured endothelial cells (EC; porcine aorta and human umbilical vein). Deformation of both native and cultured endothelial cells for 6 h resulted in a marked increase in ET-I synthesis which was preceded by a transient (30-60 min) activation of transcription factors activator protein-1 (AP-1) and CCAAT/enhancer-bindingprotein (C/EBP) beta and/or 6. A decoy oligodeoxynucleotide directed against AP-1 inhibited deformation-induced ppET-1 expression in the rabbit jugular vein as well as in porcine aorta EC and human umbilical vein EC but not in the rabbit carotid artery. Subsequent reporter gene analyses with different rat ppET-1 promoter-luciferase constructs transiently transfected into porcine aorta EC identified a single AP-1 binding site at -110 to -100 bp as the primary response element for deformation-induced ppET-1 expression. Moreover, a C/EBP-specific decoy oligodeoxynucleotide abolished ppET-1 expression in the endothelium of the rabbit carotid artery, but not in the jugular vein where basal ET-1 synthesis was greatly enhanced instead. These findings suggest that the key transcription factors controlling deformation-induced ppET-1 expression in endothelial cells are blood vessel rather than species-specific. In humans, adjunct treatment with an AP-1-specific decoy oligodeoxynucleotide may prove be an interesting gene therapeutic option for the above cardiovascular interventions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 17:56:37