Gene deletion of dopamine beta-hydroxylase and alpha1-adrenoceptors demonstrates involvement of catecholamines in vascular remodeling.

Détails

ID Serval
serval:BIB_8483244F1166
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Gene deletion of dopamine beta-hydroxylase and alpha1-adrenoceptors demonstrates involvement of catecholamines in vascular remodeling.
Périodique
American Journal of Physiology. Heart and Circulatory Physiology
Auteur(s)
Zhang H., Cotecchia S., Thomas S.A., Tanoue A., Tsujimoto G., Faber J.E.
ISSN
0363-6135 (Print)
ISSN-L
0363-6135
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
287
Numéro
5
Pages
H2106-H2114
Langue
anglais
Résumé
In vitro studies have shown that stimulation of alpha1-adrenoceptors (ARs) directly induces proliferation, hypertrophy, and migration of arterial smooth muscle cells and adventitial fibroblasts. In vivo studies confirmed these findings and showed that catecholamine trophic activity becomes excessive after experimental balloon injury and contributes to neointimal growth, adventitial thickening, and lumen loss. However, past studies have been limited by selectivity of pharmacological agents. The aim of this study, in which mice devoid of norepinephrine and epinephrine synthesis [dopamine beta-hydroxylase (DBH-/-)] or deficient in alpha1-AR subtypes expressed in murine carotid (alpha1B-AR-/- and alpha1D-AR-/-) were used, was to test the hypothesis that catecholamines contribute to wall hypertrophy after injury. At 3 wk after injury of wild-type mice, lumen area and carotid circumference increased significantly, and hypertrophy of media and adventitia was in excess of that needed to restore circumferential wall stress to normal. In DBH-/- and alpha1B-AR-/- mice, increases in lumen area, circumference, and hypertrophy of the media and adventitia were reduced by 50-91%, resulting in restoration of wall tension to nearly normal (DBH-/-) or normal (alpha1B-AR-/-). In contrast, in alpha1D-AR-/- mice, increases in lumen area, circumference, and wall hypertrophy were unaffected and wall thickening remained in excess of that required to return tension to normal. When examined 5 days after injury, proliferation and leukocyte infiltration were inhibited in DBH-/- mice. These studies suggest that the trophic effects of catecholamines are mediated primarily by alpha1B-ARs in mouse carotid and contribute to hypertrophic growth after vascular injury.
Mots-clé
Animals, Apoptosis, Carotid Arteries/metabolism, Carotid Arteries/pathology, Carotid Artery Injuries/metabolism, Carotid Artery Injuries/pathology, Catecholamines/metabolism, Cell Division, Dopamine beta-Hydroxylase/genetics, Female, Gene Deletion, Leukocytes/pathology, Male, Mice, Mice, Knockout, Protein Isoforms/genetics, Protein Isoforms/metabolism, Receptors, Adrenergic, alpha-1/genetics, Receptors, Adrenergic, alpha-1/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 14:44
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