TY - JOUR
T1 - Ischemic neoangiogenesis enhanced by β2-adrenergic receptor overexpression
T2 - A novel role for the endothelial adrenergic system
AU - Iaccarino, Guido
AU - Ciccarelli, Michele
AU - Sorriento, Daniela
AU - Galasso, Gennaro
AU - Campanile, Alfonso
AU - Santulli, Gaetano
AU - Cipolletta, Ersilia
AU - Cerullo, Vincenzo
AU - Cimini, Vincenzo
AU - Altobelli, Giovanna Giuseppina
AU - Piscione, Federico
AU - Priante, Ornella
AU - Pastore, Lucio
AU - Chiariello, Massimo
AU - Salvatore, Francesco
AU - Koch, Walter J.
AU - Trimarco, Bruno
PY - 2005/11
Y1 - 2005/11
N2 - β2-Adrenergic receptors (β2ARs) are widely expressed, although their physiological relevance in many tissues is not yet fully understood. In vascular endothelial cells, they regulate NO release and vessel tone. Here we provide novel evidence that β2ARs can regulate neoangiogenesis in response to chronic ischemia. We used in vivo adenoviral-mediated gene transfer of the human β2AR to the endothelium of the rat femoral artery and increased β2AR signaling resulting in ameliorated angiographic blood flow and hindlimb perfusion after chronic ischemia. Histological analysis confirmed that β2AR overexpression also produced benefits on capillary density. The same maneuver partially rescued impaired angiogenesis in spontaneously hypertensive rats (SHR), whereas gene delivery of the G-protein-coupling defective mutant Ile164 β2AR failed to provide ameliorations. Stimulation of endogenous and overexpressed β2AR on endothelial cells in vitro was found to regulate cell number by inducing proliferation and [3H]-thymidine incorporation through means of extracellular receptor-activated kinase and vascular endothelial growth factor. The β2AR also has novel effects on endothelial cell number through stimulation of proapoptosis and antiapoptosis pathways involving p38 mitogen-activated protein kinase and PI3-kinase/Akt activation. Therefore, β2ARs play a critical role in endothelial cell proliferation and function including revascularization, suggesting a novel and physiologically relevant role in neoangiogenesis in response to ischemia.
AB - β2-Adrenergic receptors (β2ARs) are widely expressed, although their physiological relevance in many tissues is not yet fully understood. In vascular endothelial cells, they regulate NO release and vessel tone. Here we provide novel evidence that β2ARs can regulate neoangiogenesis in response to chronic ischemia. We used in vivo adenoviral-mediated gene transfer of the human β2AR to the endothelium of the rat femoral artery and increased β2AR signaling resulting in ameliorated angiographic blood flow and hindlimb perfusion after chronic ischemia. Histological analysis confirmed that β2AR overexpression also produced benefits on capillary density. The same maneuver partially rescued impaired angiogenesis in spontaneously hypertensive rats (SHR), whereas gene delivery of the G-protein-coupling defective mutant Ile164 β2AR failed to provide ameliorations. Stimulation of endogenous and overexpressed β2AR on endothelial cells in vitro was found to regulate cell number by inducing proliferation and [3H]-thymidine incorporation through means of extracellular receptor-activated kinase and vascular endothelial growth factor. The β2AR also has novel effects on endothelial cell number through stimulation of proapoptosis and antiapoptosis pathways involving p38 mitogen-activated protein kinase and PI3-kinase/Akt activation. Therefore, β2ARs play a critical role in endothelial cell proliferation and function including revascularization, suggesting a novel and physiologically relevant role in neoangiogenesis in response to ischemia.
KW - Angiogenesis
KW - Hypertension
KW - In vivo digital angiography
KW - Polymorphism
KW - Rats
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U2 - 10.1161/01.RES.0000191541.06788.bb
DO - 10.1161/01.RES.0000191541.06788.bb
M3 - Article
C2 - 16239589
AN - SCOPUS:33644693118
SN - 0009-7330
VL - 97
SP - 1182
EP - 1189
JO - Circulation research
JF - Circulation research
IS - 11
ER -