AJP - Heart Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 287: H2376-H2383, 2004. First published July 22, 2004; doi:10.1152/ajpheart.01173.2003
0363-6135/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/6/H2376    most recent
01173.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (16)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, X.
Right arrow Articles by Hall, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, X.
Right arrow Articles by Hall, J. L.

LDL receptor-related protein LRP6 regulates proliferation and survival through the Wnt cascade in vascular smooth muscle cells

Xiaohong Wang, Neeta Adhikari, Qinglu Li, and Jennifer L. Hall

Lillehei Heart Institute, Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455

Submitted 15 December 2003 ; accepted in final form 20 July 2004

Initial studies have established expression of low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) in vascular smooth muscle cells (VSMCs). We hypothesized that LRP6 is a critical mediator governing the regulation of the canonical Wnt/{beta}-catenin/T cell factor 4 (Tcf-4) cascade in the vasculature. This hypothesis was based on our previous work demonstrating a role for the {beta}-catenin/Tcf-4 pathway in vascular remodeling as well as work in other cell systems establishing a role for LRP family members in the Wnt cascade. In line with our hypothesis, LRP6 upregulation significantly increased Wnt-1-induced Tcf activation. Moreover, a dominant interfering LRP6 mutant lacking the carboxyl intracellular domain (LRP6{Delta}C) abolished Tcf activity. LRP6-induced stimulation of Tcf was blocked in VSMCs harboring constitutive expression of a dominant negative Tcf-4 transgene lacking the {beta}-catenin binding domain, suggesting that LRP6-induced activation of Tcf was mediated through a {beta}-catenin-dependent signal. Expression of the dominant interfering LRP6{Delta}C transgene was sufficient to abolish the Wnt-induced survival as well as cyclin D1 activity and cell cycle progression. In conclusion, these findings provide the first evidence of a role for an LDL receptor-related protein in the regulation of VSMC proliferation and survival through the evolutionary conserved Wnt signaling cascade.

{beta}-catenin; apoptosis; cyclin D1; T cell factor-4


Address for reprint requests and other correspondence: J. L. Hall, Lillehei Heart Institute, Univ. of Minnesota, 420 Delaware St., Minneapolis, MN 55455 (E-mail: Hallx068{at}umn.edu)




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
A. Giordano, S. Romano, M. Mallardo, A. D'Angelillo, G. Cali, N. Corcione, P. Ferraro, and M. F. Romano
FK506 can activate transforming growth factor-{beta} signalling in vascular smooth muscle cells and promote proliferation
Cardiovasc Res, August 1, 2008; 79(3): 519 - 526.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
S. J. George
Wnt Pathway: A New Role in Regulation of Inflammation
Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 400 - 402.
[Full Text] [PDF]

Home page
 Circ. Res.Home page
T. Couffinhal, P. Dufourcq, and C. Duplaa
{beta}-Catenin Nuclear Activation: Common Pathway Between Wnt and Growth Factor Signaling in Vascular Smooth Muscle Cell Proliferation?
Circ. Res., December 8, 2006; 99(12): 1287 - 1289.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
X. Wang, Q. Hu, A. Mansoor, J. Lee, Z. Wang, T. Lee, A. H. L. From, and J. Zhang
Bioenergetic and functional consequences of stem cell-based VEGF delivery in pressure-overloaded swine hearts
Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1393 - H1405.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. L. Haines, N. Schnetz-Boutaud, S. Schmidt, W. K. Scott, A. Agarwal, E. A. Postel, L. Olson, S. J. Kenealy, M. Hauser, J. R. Gilbert, et al.
Functional Candidate Genes in Age-Related Macular Degeneration: Significant Association with VEGF, VLDLR, and LRP6
Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 329 - 335.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Rahmani, J. T. Read, J. M. Carthy, P. C. McDonald, B. W. Wong, M. Esfandiarei, X. Si, Z. Luo, H. Luo, P. S. Rennie, et al.
Regulation of the Versican Promoter by the {beta}-Catenin-T-cell Factor Complex in Vascular Smooth Muscle Cells
J. Biol. Chem., April 1, 2005; 280(13): 13019 - 13028.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.