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Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells
Experimental & Molecular Medicine ; : 588-600, 2005.
Artículo en Inglés | WPRIM | ID: wpr-191492
ABSTRACT
Prostaglandin E2(PGE2), a major product of cyclooxygenase, has been implicated in modulating angiogenesis, vascular function, and inflammatory processes, but the underlying mechanism is not clearly elucidated. We here investigated the molecular mechanism by which PGE 2 regulates angiogenesis. Treatment of human umbilical vein endothelial cells (HUVEC) with PGE 2 increased angiogenesis. PGE 2 increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), eNOS activity, and nitric oxide (NO) production by the activation of cAMP-dependent protein kinase (PKA) and phosphatidylinositol 3-kinase (PI3K). Dibutyryl cAMP (DB-cAMP) mimicked the role of PGE 2 in angiogenesis and the signaling pathway, suggesting that cAMP is a down-stream mediator of PGE 2. Furthermore, PGE 2 increased endothelial cell sprouting from normal murine aortic segments, but not from eNOS-deficient ones, on Matrigel. The angiogenic effects of PGE 2 were inhibited by the inhibitors of PKA, PI3K, eNOS, and soluble guanylate cyclase, but not by phospholipase C inhibitor. These results clearly show that PGE 2 increased angiogenesis by activating the NO/cGMP signaling pathway through PKA/PI3K/Akt-dependent increase in eNOS activity.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Aorta / Fosforilación / Venas Umbilicales / Dinoprostona / Transducción de Señal / Movimiento Celular / Ratas Sprague-Dawley / Ratones Noqueados / AMP Cíclico / GMP Cíclico Límite: Animales / Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2005 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Aorta / Fosforilación / Venas Umbilicales / Dinoprostona / Transducción de Señal / Movimiento Celular / Ratas Sprague-Dawley / Ratones Noqueados / AMP Cíclico / GMP Cíclico Límite: Animales / Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2005 Tipo del documento: Artículo