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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|
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|
|
|
|
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|
|
|
|
 |
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|
|
|
|
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|
|
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|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 G. Hu, J. Tang, B. Zhang, Y. Lin, J.-i. Hanai, J. Galloway, V. Bedell, N. Bahary, Z. Han, R. Ramchandran, et al. A novel endothelial-specific heat shock protein HspA12B is required in both zebrafish development and endothelial functions in vitro J. Cell Sci., October 1, 2006; 119(19): 4117 - 4126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
C. J. Lowenstein Integrin-Linked Kinase Plays a Key Role in Coxsackievirus Replication Circ. Res., August 18, 2006; 99(4): 346 - 347. [Full Text] [PDF]
|
|
|
|
|
|
R. D. Balsara, F. J. Castellino, and V. A. Ploplis A Novel Function of Plasminogen Activator Inhibitor-1 in Modulation of the AKT Pathway in Wild-type and Plasminogen Activator Inhibitor-1-deficient Endothelial Cells J. Biol. Chem., August 11, 2006; 281(32): 22527 - 22536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dance, A. Montagner, A. Yart, B. Masri, Y. Audigier, B. Perret, J.-P. Salles, and P. Raynal The Adaptor Protein Gab1 Couples the Stimulation of Vascular Endothelial Growth Factor Receptor-2 to the Activation of Phosphoinositide 3-Kinase J. Biol. Chem., August 11, 2006; 281(32): 23285 - 23295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wei and Y. Xia Proteasome Inhibition Down-regulates Endothelial Nitric-oxide Synthase Phosphorylation and Function J. Biol. Chem., August 4, 2006; 281(31): 21652 - 21659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fitau, G. Boulday, F. Coulon, T. Quillard, and B. Charreau The Adaptor Molecule Lnk Negatively Regulates Tumor Necrosis Factor-{alpha}-dependent VCAM-1 Expression in Endothelial Cells through Inhibition of the ERK1 and -2 Pathways J. Biol. Chem., July 21, 2006; 281(29): 20148 - 20159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Boodhwani, Y. Nakai, P. Voisine, J. Feng, J. Li, S. Mieno, B. Ramlawi, C. Bianchi, R. Laham, and F. W. Sellke High-Dose Atorvastatin Improves Hypercholesterolemic Coronary Endothelial Dysfunction Without Improving the Angiogenic Response Circulation, July 4, 2006; 114(1_suppl): I-402 - I-408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 X. Du, I. Kristiana, J. Wong, and A. J. Brown Involvement of Akt in ER-to-Golgi Transport of SCAP/SREBP: A Link between a Key Cell Proliferative Pathway and Membrane Synthesis Mol. Biol. Cell, June 1, 2006; 17(6): 2735 - 2745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Izumiya, I. Shiojima, K. Sato, D. B. Sawyer, W. S. Colucci, and K. Walsh Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload Hypertension, May 1, 2006; 47(5): 887 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Ryter, J. Alam, and A. M. K. Choi Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications Physiol Rev, April 1, 2006; 86(2): 583 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nishimura, W. Li, Y. Hoshino, T. Kadohama, H. Asada, S. Ohgi, and B. E. Sumpio Role of AKT in cyclic strain-induced endothelial cell proliferation and survival Am J Physiol Cell Physiol, March 1, 2006; 290(3): C812 - C821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hasegawa, H. Takano, K. Iwanaga, M. Ohtsuka, Y. Qin, Y. Niitsuma, K. Ueda, T. Toyoda, H. Tadokoro, and I. Komuro Cardioprotective Effects of Granulocyte Colony-Stimulating Factor in Swine With Chronic Myocardial Ischemia J. Am. Coll. Cardiol., February 21, 2006; 47(4): 842 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|