Adenylate Cyclase/Protein Kinase A Signaling Pathway Enhances Angiogenesis Through Induction of Vascular Endothelial Growth Factor In Vivo
| Autor: | Hideki Amano, Satoshi Minamida, Michiko Ogino, Izumi Hayashi, Hirokuni Yoshimura, Kao Ando, Masataka Majima, Shohei Yamashina |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Angiogenesis Neovascularization Physiologic Endothelial Growth Factors Biology Pharmacology Amrinone Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Cyclic AMP medicine Animals Protein kinase A signaling Protein kinase A Lymphokines Sulfonamides Forskolin Vascular Endothelial Growth Factors Adenine Prostaglandins E Isoquinolines Cyclic AMP-Dependent Protein Kinases H-89 Rats Vascular endothelial growth factor Endocrinology chemistry Signal transduction Adenylyl Cyclases medicine.drug |
| Zdroj: | Japanese Journal of Pharmacology. 87:181-188 |
| ISSN: | 0021-5198 |
| Popis: | We previously reported that endogenous prostaglandins (PGs) may increase cAMP facilitated angiogenesis through the induction of vascular endothelial growth factor (VEGF) in rat sponge implantation models. In the present experiment, we tested whether or not adenylate cyclase / protein kinase A (AC/PKA)-dependent VEGF induction enhanced angiogenesis in this model. Topical daily injections of 8-bromo-cAMP enhanced angiogenesis in a dose-dependent manner. Forskolin, an activator of AC, also facilitated angiogenesis as did amrinone, an inhibitor of phosphodiesterase. VEGF induction was confirmed by the increased levels in the fluids in the sponge matrix after topical injection of 8-bromo-cAMP. Immunohistochemical investigation further revealed the VEGF-expressed cells in the sponge granulation tissues to be fibroblasts, and the intensity of positive reactions was enhanced by 8-bromo-cAMP, forskolin and amrinone. Angiogenesis without topical injections of the above compounds was suppressed by SQ22,536, an inhibitor for AC, or H-89, an inhibitor for PKA, with concomitant reductions in VEGF levels. Daily topical injections of neutralizing antibody or anti-sense oligonucleotide against VEGF significantly suppressed angiogenesis. PGE2-induced angiogenesis was suppressed with SQ22,536 or H-89. These results suggested that AC/PKA-dependent induction of VEGF certainly enhanced angiogenesis and that pharmacological tools for controlling this signaling pathway may be able to facilitate the management of conditions involving angiogenesis. |
| Databáze: | OpenAIRE |
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