Published online before print May 26, 2005, doi: 10.1161/01.RES.0000171894.03801.03
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 3, 2003
Revised on May 17, 2005
Accepted on May 18, 2005
Angiopoietin-1 Opposes VEGF-Induced Increase in Endothelial Permeability by Inhibiting TRPC1-Dependent Ca2+ Influx
David Jho ;
From the Department of Pharmacology and The Center of Lung and Vascular Biology, The University of Illinois, Chicago.
* To whom correspondence should be addressed. E-mail: abmalik{at}uic.edu.
Angiopoietin-1 (Ang1) exerts a vascular endothelial barrier protective effect by blocking the action of permeability-increasing mediators such as vascular endothelial growth factor (VEGF) through unclear mechanisms. Because VEGF may signal endothelial hyperpermeability through the phospholipase C (PLC)-IP3 pathway that activates extracellular Ca2+ entry via the plasmalemmal store-operated channel transient receptor potential canonical-1 (TRPC1), we addressed the possibility that Ang1 acts by inhibiting this Ca2+ entry mechanism in endothelial cells. Studies in endothelial cell monolayers demonstrated that Ang1 inhibited the VEGF-induced Ca2+ influx and increase in endothelial permeability in a concentration-dependent manner. Inhibitors of the PLC-IP3 Ca2+ signaling pathway prevented the VEGF-induced Ca2+ influx and hyperpermeability similar to the inhibitory effects seen with Ang1. Ang1 had no effect on PLC phosphorylation and IP3 production, thus its permeability-decreasing effect could not be ascribed to inhibition of PLC activation. However, Ang1 interfered with downstream IP3-dependent plasmalemmal Ca2+ entry without affecting the release of intracellular Ca2+ stores. Anti-TRPC1 antibody inhibited the VEGF-induced Ca2+ entry and the increased endothelial permeability. TRPC1 overexpression in endothelial cells augmented the VEGF-induced Ca2+ entry, and application of Ang1 opposed this effect. In immunoprecipitation studies, Ang1 inhibited the association of IP3 receptor (IP3R) and TRPC1, consistent with the coupling hypothesis of Ca2+ entry. These results demonstrate that Ang1 blocks the TRPC1-dependent Ca2+ influx induced by VEGF by interfering with the interaction of IP3R with TRPC1, and thereby abrogates the increase in endothelial permeability.
Key words: endothelial permeability • vascular endothelial growth factor • angiopoietin-1 • Ca2+ influx • transient receptor potential channel
This article has been cited by other articles:
 |
|
 |
|
  M. Oubaha and J.-P. Gratton Phosphorylation of endothelial nitric oxide synthase by atypical PKC{zeta} contributes to angiopoietin-1-dependent inhibition of VEGF-induced endothelial permeability in vitro Blood, October 8, 2009; 114(15): 3343 - 3351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Jung, D. H. Kim, A. S. Lee, S. Lee, K. P. Kang, S. Y. Lee, K. Y. Jang, M. J. Sung, S. K. Park, and W. Kim Peritubular capillary preservation with COMP-angiopoietin-1 decreases ischemia-reperfusion-induced acute kidney injury Am J Physiol Renal Physiol, October 1, 2009; 297(4): F952 - F960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, M. Stankovic, B. P.-L. Lee, M. Aurrand-Lions, C. N. Hahn, Y. Lu, B. A. Imhof, M. A. Vadas, and J. R. Gamble JAM-C Induces Endothelial Cell Permeability Through Its Association and Regulation of {beta}3 Integrins Arterioscler Thromb Vasc Biol, August 1, 2009; 29(8): 1200 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Ng, M. D. McCormack, J. A. Airey, C. A. Singer, P. S. Keller, X.-M. Shen, and J. R. Hume TRPC1 and STIM1 mediate capacitative Ca2+ entry in mouse pulmonary arterial smooth muscle cells J. Physiol., June 1, 2009; 587(11): 2429 - 2442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. F. Abdullaev, J. M. Bisaillon, M. Potier, J. C. Gonzalez, R. K. Motiani, and M. Trebak Stim1 and Orai1 Mediate CRAC Currents and Store-Operated Calcium Entry Important for Endothelial Cell Proliferation Circ. Res., November 21, 2008; 103(11): 1289 - 1299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M van der Heijden, G P van Nieuw Amerongen, P Koolwijk, V W M van Hinsbergh, and A B J Groeneveld Angiopoietin-2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic critically ill patients Thorax, October 1, 2008; 63(10): 903 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Foster, S. C. Slater, J. Seckley, D. Kerjaschki, D. O. Bates, P. W. Mathieson, and S. C. Satchell Vascular Endothelial Growth Factor-C, a Potential Paracrine Regulator of Glomerular Permeability, Increases Glomerular Endothelial Cell Monolayer Integrity and Intracellular Calcium Am. J. Pathol., October 1, 2008; 173(4): 938 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. N. Gavrilovskaya, E. E. Gorbunova, N. A. Mackow, and E. R. Mackow Hantaviruses Direct Endothelial Cell Permeability by Sensitizing Cells to the Vascular Permeability Factor VEGF, while Angiopoietin 1 and Sphingosine 1-Phosphate Inhibit Hantavirus-Directed Permeability J. Virol., June 15, 2008; 82(12): 5797 - 5806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Childs, B. Tharakan, N. Byrge, J. H. Tinsley, F. A. Hunter, and W. R. Smythe Angiopoietin-1 inhibits intrinsic apoptotic signaling and vascular hyperpermeability following hemorrhagic shock Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2285 - H2295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, M. Stankovic, C. S. Bonder, C. N. Hahn, M. Parsons, S. M. Pitson, P. Xia, R. L. Proia, M. A. Vadas, and J. R. Gamble Basal and angiopoietin-1-mediated endothelial permeability is regulated by sphingosine kinase-1 Blood, April 1, 2008; 111(7): 3489 - 3497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Mammoto, S. M. Parikh, A. Mammoto, D. Gallagher, B. Chan, G. Mostoslavsky, D. E. Ingber, and V. P. Sukhatme Angiopoietin-1 Requires p190 RhoGAP to Protect against Vascular Leakage in Vivo J. Biol. Chem., August 17, 2007; 282(33): 23910 - 23918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Brissova, A. Shostak, M. Shiota, P. O. Wiebe, G. Poffenberger, J. Kantz, Z. Chen, C. Carr, W. G. Jerome, J. Chen, et al. Pancreatic Islet Production of Vascular Endothelial Growth Factor-A Is Essential for Islet Vascularization, Revascularization, and Function Diabetes, November 1, 2006; 55(11): 2974 - 2985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Remillard and J. X.-J. Yuan Transient Receptor Potential Channels and Caveolin-1: Good Friends in Tight Spaces Mol. Pharmacol., October 1, 2006; 70(4): 1151 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Hong, F. Hong, A. Olschewski, J. A. Cabrera, A. Varghese, D. P. Nelson, and E. K. Weir Role of Store-Operated Calcium Channels and Calcium Sensitization in Normoxic Contraction of the Ductus Arteriosus Circulation, September 26, 2006; 114(13): 1372 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-W. Cheng, A.F. James, R.R. Foster, J.C. Hancox, and D.O. Bates VEGF Activates Receptor-Operated Cation Channels in Human Microvascular Endothelial Cells Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1768 - 1776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Adamson and F. E. Curry Ang-1: Tie-ing up endothelial adhesion? Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H74 - H76. [Full Text] [PDF]
|
|
|
|
|
|
X. Yao and C. J. Garland Recent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels Circ. Res., October 28, 2005; 97(9): 853 - 863. [Abstract] [Full Text] [PDF]
|
|