Circulation Research. 2002;90:1243-1250
doi: 10.1161/01.RES.0000022200.71892.9F
doi: 10.1161/01.RES.0000022200.71892.9F
© 2002 American Heart Association, Inc.
Review |
Role of Akt Signaling in Vascular Homeostasis and Angiogenesis
From the Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass.
Correspondence to Kenneth Walsh, PhD, Molecular Cardiology/CVI, Boston University School of Medicine, 715 Albany St, W611, Boston, MA 02118. E-mail kwalsh{at}world.std.com
Akt is a serine/threonine protein kinase that is activated by a number of growth factors and cytokines in a phosphatidylinositol-3 kinase–dependent manner. Although antiapoptotic activity of Akt is well known, it also regulates other aspects of cellular functions, including migration, glucose metabolism, and protein synthesis. In this review, Akt signaling in endothelial cells and its critical roles in the regulation of vascular homeostasis and angiogenesis will be discussed.
Key Words: Akt • endothelial cells • angiogenesis • statins • endothelial nitric oxide synthase
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T. Watanabe, J. Suzuki, H. Yamawaki, V. K. Sharma, S.-S. Sheu, and B. C. Berk Losartan Metabolite EXP3179 Activates Akt and Endothelial Nitric Oxide Synthase via Vascular Endothelial Growth Factor Receptor-2 in Endothelial Cells: Angiotensin II Type 1 Receptor-Independent Effects of EXP3179 Circulation, September 20, 2005; 112(12): 1798 - 1805. [Abstract] [Full Text] [PDF]
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M. Li, K.-R. Chiou, A. Bugayenko, K. Irani, and D. A. Kass Reduced Wall Compliance Suppresses Akt-Dependent Apoptosis Protection Stimulated by Pulse Perfusion Circ. Res., September 16, 2005; 97(6): 587 - 595. [Abstract] [Full Text] [PDF]
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T. Maffucci, E. Piccolo, A. Cumashi, M. Iezzi, A. M. Riley, A. Saiardi, H. Y. Godage, C. Rossi, M. Broggini, S. Iacobelli, et al. Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway by Inositol Pentakisphosphate Results in Antiangiogenic and Antitumor Effects Cancer Res., September 15, 2005; 65(18): 8339 - 8349. [Abstract] [Full Text] [PDF]
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F. C. Sasso, D. Torella, O. Carbonara, G. M. Ellison, M. Torella, M. Scardone, C. Marra, R. Nasti, R. Marfella, D. Cozzolino, et al. Increased Vascular Endothelial Growth Factor Expression But Impaired Vascular Endothelial Growth Factor Receptor Signaling in the Myocardium of Type 2 Diabetic Patients With Chronic Coronary Heart Disease J. Am. Coll. Cardiol., September 6, 2005; 46(5): 827 - 834. [Abstract] [Full Text] [PDF]
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 S. Murakami, N. Nagaya, T. Itoh, T. Iwase, T. Fujisato, K. Nishioka, K. Hamada, K. Kangawa, and H. Kimura Adrenomedullin Regenerates Alveoli and Vasculature in Elastase-induced Pulmonary Emphysema in Mice Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 581 - 589. [Abstract] [Full Text] [PDF]
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K. Hamada, T. Sasaki, P. A. Koni, M. Natsui, H. Kishimoto, J. Sasaki, N. Yajima, Y. Horie, G. Hasegawa, M. Naito, et al. The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis Genes & Dev., September 1, 2005; 19(17): 2054 - 2065. [Abstract] [Full Text] [PDF]
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M.-T. Huang, J. C. Mason, G. M. Birdsey, V. Amsellem, N. Gerwin, D. O. Haskard, A. J. Ridley, and A. M. Randi Endothelial intercellular adhesion molecule (ICAM)-2 regulates angiogenesis Blood, September 1, 2005; 106(5): 1636 - 1643. [Abstract] [Full Text] [PDF]
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M. Eto, A. Kouroedov, F. Cosentino, and T. F. Luscher Glycogen Synthase Kinase-3 Mediates Endothelial Cell Activation by Tumor Necrosis Factor-{alpha} Circulation, August 30, 2005; 112(9): 1316 - 1322. [Abstract] [Full Text] [PDF]
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 H. S. Rugo, R. S. Herbst, G. Liu, J. W. Park, M. S. Kies, H. M. Steinfeldt, Y. K. Pithavala, S. D. Reich, J. L. Freddo, and G. Wilding Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results J. Clin. Oncol., August 20, 2005; 23(24): 5474 - 5483. [Abstract] [Full Text] [PDF]
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H. Hu, C. Jiang, G. Li, and J. Lu PKB/AKT and ERK regulation of caspase-mediated apoptosis by methylseleninic acid in LNCaP prostate cancer cells Carcinogenesis, August 1, 2005; 26(8): 1374 - 1381. [Abstract] [Full Text] [PDF]
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K. D. Puri, T. A. Doggett, C.-Y. Huang, J. Douangpanya, J. S. Hayflick, M. Turner, J. Penninger, and T. G. Diacovo The role of endothelial PI3K{gamma} activity in neutrophil trafficking Blood, July 1, 2005; 106(1): 150 - 157. [Abstract] [Full Text] [PDF]
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D. A. Kass Ventricular Arterial Stiffening: Integrating the Pathophysiology Hypertension, July 1, 2005; 46(1): 185 - 193. [Abstract] [Full Text] [PDF]
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J. P. Huddleson, N. Ahmad, S. Srinivasan, and J. B Lingrel Induction of KLF2 by Fluid Shear Stress Requires a Novel Promoter Element Activated by a Phosphatidylinositol 3-Kinase-dependent Chromatin-remodeling Pathway J. Biol. Chem., June 17, 2005; 280(24): 23371 - 23379. [Abstract] [Full Text] [PDF]
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R. I. Feldman, J. M. Wu, M. A. Polokoff, M. J. Kochanny, H. Dinter, D. Zhu, S. L. Biroc, B. Alicke, J. Bryant, S. Yuan, et al. Novel Small Molecule Inhibitors of 3-Phosphoinositide-dependent Kinase-1 J. Biol. Chem., May 20, 2005; 280(20): 19867 - 19874. [Abstract] [Full Text] [PDF]
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S. J. Zieman, V. Melenovsky, and D. A. Kass Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 932 - 943. [Abstract] [Full Text] [PDF]
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F. Li and K. U. Malik Angiotensin II-induced Akt activation is mediated by metabolites of arachidonic acid generated by CaMKII-stimulated Ca2+-dependent phospholipase A2 Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2306 - H2316. [Abstract] [Full Text] [PDF]
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V. Limaye, X. Li, C. Hahn, P. Xia, M. C. Berndt, M. A. Vadas, and J. R. Gamble Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members Blood, April 15, 2005; 105(8): 3169 - 3177. [Abstract] [Full Text] [PDF]
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 F. Li and K. U. Malik Angiotensin II-Induced Akt Activation through the Epidermal Growth Factor Receptor in Vascular Smooth Muscle Cells Is Mediated by Phospholipid Metabolites Derived by Activation of Phospholipase D J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1043 - 1054. [Abstract] [Full Text] [PDF]
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T. Fujii, N. Nagaya, T. Iwase, S. Murakami, Y. Miyahara, K. Nishigami, H. Ishibashi-Ueda, M. Shirai, T. Itoh, K. Ishino, et al. Adrenomedullin enhances therapeutic potency of bone marrow transplantation for myocardial infarction in rats Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1444 - H1450. [Abstract] [Full Text] [PDF]
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C. Skurk, H. Maatz, E. Rocnik, A. Bialik, T. Force, and K. Walsh Glycogen-Synthase Kinase3{beta}/{beta}-Catenin Axis Promotes Angiogenesis Through Activation of Vascular Endothelial Growth Factor Signaling in Endothelial Cells Circ. Res., February 18, 2005; 96(3): 308 - 318. [Abstract] [Full Text] [PDF]
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 M. Bosch-Marce, R. Pola, A. B Wecker, M. Silver, A. Weber, C. Luedemann, C. Curry, T. Murayama, M. Kearney, Y.-s. Yoon, et al. Hyperhomocyst(e)inemia impairs angiogenesis in a murine model of limb ischemia Vascular Medicine, February 1, 2005; 10(1): 15 - 22. [Abstract] [PDF]
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J.-Y. Paik, K.-H. Lee, B.-H. Ko, Y. S. Choe, Y. Choi, and B.-T. Kim Nitric Oxide Stimulates 18F-FDG Uptake in Human Endothelial Cells Through Increased Hexokinase Activity and GLUT1 Expression J. Nucl. Med., February 1, 2005; 46(2): 365 - 370. [Abstract] [Full Text] [PDF]
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 E. V. Gerasimovskaya, D. A. Tucker, and K. R. Stenmark Activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin is necessary for hypoxia-induced pulmonary artery adventitial fibroblast proliferation J Appl Physiol, February 1, 2005; 98(2): 722 - 731. [Abstract] [Full Text] [PDF]
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H. Ogawa, D. G. Binion, J. Heidemann, M. Theriot, P. J. Fisher, N. A. Johnson, M. F. Otterson, and P. Rafiee Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells Am J Physiol Cell Physiol, February 1, 2005; 288(2): C272 - C281. [Abstract] [Full Text] [PDF]
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 J. F. Sun, T. Phung, I. Shiojima, T. Felske, J. N. Upalakalin, D. Feng, T. Kornaga, T. Dor, A. M. Dvorak, K. Walsh, et al. Microvascular patterning is controlled by fine-tuning the Akt signal PNAS, January 4, 2005; 102(1): 128 - 133. [Abstract] [Full Text] [PDF]
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 C. Stirone, A. Boroujerdi, S. P. Duckles, and D. N. Krause Estrogen Receptor Activation of Phosphoinositide-3 Kinase, Akt, and Nitric Oxide Signaling in Cerebral Blood Vessels: Rapid and Long-Term Effects Mol. Pharmacol., January 1, 2005; 67(1): 105 - 113. [Abstract] [Full Text] [PDF]
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