Donate Help Contact The AHA Sign In Home
American Heart Association
Arteriosclerosis, Thrombosis, and Vascular Biology
Search: search_blue_button Advanced Search
Published Online
on October 26, 2006

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006
Published online before print October 26, 2006, doi: 10.1161/01.ATV.0000250972.83623.61
A more recent version of this article appeared on January 1, 2007
This Article
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow All Versions of this Article:
27/1/63    most recent
01.ATV.0000250972.83623.61v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Piqueras, L.
Right arrow Articles by Bishop-Bailey, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Piqueras, L.
Right arrow Articles by Bishop-Bailey, D.

Submitted on May 16, 2006
Accepted on October 10, 2006

Activation of PPAR{beta}/{delta} Induces Endothelial Cell Proliferation and Angiogenesis

Laura Piqueras ; Andrew R. Reynolds ; Kairbaan M. Hodivala-Dilke ; Arántzazu Alfranca ; Juan M. Redondo ; Toshihisa Hatae ; Tadashi Tanabe ; Timothy D. Warner ; and David Bishop-Bailey *

From Cardiac, Vascular & Inflammation Research (L.P., T.D.W., D.B.-B.), William Harvey Research Institute; T Cell Adhesion and Disease Group (A.R.R., K.M.H.-D.), Centre for Tumour Biology, Institute of Cancer, and the CR-UK Clinical Centre, Barts, and The London, Queen Mary University London, Charterhouse Sq, London, UK; Centro de Biologia Molecular Severo Ochoa (A.A., J.M.R.), Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Autonoma de Madrid, Facultad de Ciencias, Cantoblanco, Spain; Department of Pharmacology (T.H., T.T.), National Cardiovascular Center Research Institute, Fujishiro-dai, Suita, Osaka, Japan.

* To whom correspondence should be addressed. E-mail: d.bishop-bailey{at}qmul.ac.uk.

Objective--The role of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-{beta}/{delta} in endothelial cells remains unclear. Interestingly, the selective PPAR{beta}/{delta} ligand GW501516 is in phase II clinical trials for dyslipidemia. Here, using GW501516, we have assessed the involvement of PPAR{beta}/{delta} in endothelial cell proliferation and angiogenesis.

Methods and Results--Western blot analysis indicated PPAR{beta}/{delta} was expressed in primary human umbilical and aortic endothelial cells, and in the endothelial cell line, EAHy926. Treatment with GW501516 increased human endothelial cell proliferation and morphogenesis in 3-day cultures in vitro, endothelial cell outgrowth from murine aortic vessels in vitro, and angiogenesis in a murine matrigel plug assay in vivo. GW501516 induced vascular endothelial cell growth factor mRNA and peptide release, as well as adipose differentiation-related protein (ADRP), a PPAR{beta}/{delta} target gene. GW501516-induced proliferation, morphogenesis, vascular endothelial growth factor (VEGF), and ADRP were absent in endothelial cells transfected with dominant-negative PPAR{beta}/{delta}. Furthermore, treatment of cells with cyclo-VEGFI, a VEGF receptor1/2 antagonist, abolished GW501516-induced endothelial cell proliferation and tube formation.

Conclusions-- PPAR{beta}/{delta} is a novel regulator of endothelial cell proliferation and angiogenesis through VEGF. The use of GW501516 to treat dyslipidemia may need to be carefully monitored in patients susceptible to angiogenic disorders.
Key words: angiogenesis • endothelial cells • PPAR{beta}/{delta} • vascular endothelial growth factor




This article has been cited by other articles:


Home page
 FASEB J.Home page
H. Elmasri, C. Karaaslan, Y. Teper, E. Ghelfi, M. Weng, T. A. Ince, H. Kozakewich, J. Bischoff, and S. Cataltepe
Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells
FASEB J, November 1, 2009; 23(11): 3865 - 3873.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
E. Ehrenborg and A. Krook
Regulation of Skeletal Muscle Physiology and Metabolism by Peroxisome Proliferator-Activated Receptor {delta}
Pharmacol. Rev., September 1, 2009; 61(3): 373 - 393.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
H. Kwak, I. Hwang, J. H. Kim, M. Y. Kim, J. S. Yang, and S. Jeong
Modulation of transcription by the peroxisome proliferator-activated receptor {delta}-binding RNA aptamer in colon cancer cells
Mol. Cancer Ther., September 1, 2009; 8(9): 2664 - 2673.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Sun, J. D. Ritzenthaler, X. Zhong, Y. Zheng, J. Roman, and S. Han
Nicotine Stimulates PPAR{beta}/{delta} Expression in Human Lung Carcinoma Cells through Activation of PI3K/mTOR and Suppression of AP-2{alpha}
Cancer Res., August 15, 2009; 69(16): 6445 - 6453.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
K. Inoue and Z.-G. Xiong
Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway
Cardiovasc Res, August 1, 2009; 83(3): 547 - 557.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
L. Piqueras, M. J. Sanz, M. Perretti, E. Morcillo, L. Norling, J. A. Mitchell, Y. Li, and D. Bishop-Bailey
Activation of PPAR{beta}/{delta} inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release
J. Leukoc. Biol., July 1, 2009; 86(1): 115 - 122.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
B. Fan, S. Ikuyama, J.-Q. Gu, P. Wei, J.-i. Oyama, T. Inoguchi, and J. Nishimura
Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells
Am J Physiol Endocrinol Metab, July 1, 2009; 297(1): E112 - E123.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
N. Wagner, C. Jehl-Pietri, P. Lopez, J. Murdaca, C. Giordano, C. Schwartz, P. Gounon, S. N. Hatem, P. Grimaldi, and K.-D. Wagner
Peroxisome proliferator-activated receptor {beta} stimulation induces rapid cardiac growth and angiogenesis via direct activation of calcineurin
Cardiovasc Res, July 1, 2009; 83(1): 61 - 71.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. Han, J. D. Ritzenthaler, X. Sun, Y. Zheng, and J. Roman
Activation of Peroxisome Proliferator-Activated Receptor {beta}/{delta} Induces Lung Cancer Growth via Peroxisome Proliferator-Activated Receptor Coactivator {gamma}-1{alpha}
Am. J. Respir. Cell Mol. Biol., March 1, 2009; 40(3): 325 - 331.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. Schiefelbein, O. Seitz, I. Goren, J. P. Dissmann, H. Schmidt, M. Bachmann, R. Sader, G. Geisslinger, J. Pfeilschifter, and S. Frank
Keratinocyte-Derived Vascular Endothelial Growth Factor Biosynthesis Represents a Pleiotropic Side Effect of Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Troglitazone but Not Rosiglitazone and Involves Activation of p38 Mitogen-Activated Protein Kinase: Implications for Diabetes-Impaired Skin Repair
Mol. Pharmacol., October 1, 2008; 74(4): 952 - 963.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
C. Gustin, M. Van Steenbrugge, and M. Raes
LPA modulates monocyte migration directly and via LPA-stimulated endothelial cells
Am J Physiol Cell Physiol, October 1, 2008; 295(4): C905 - C914.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J.-K. Han, H.-S. Lee, H.-M. Yang, J. Hur, S.-I. Jun, J.-Y. Kim, C.-H. Cho, G.-Y. Koh, J. M. Peters, K.-W. Park, et al.
Peroxisome Proliferator-Activated Receptor-{delta} Agonist Enhances Vasculogenesis by Regulating Endothelial Progenitor Cells Through Genomic and Nongenomic Activations of the Phosphatidylinositol 3-Kinase/Akt Pathway
Circulation, September 2, 2008; 118(10): 1021 - 1033.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Gaudel, C. Schwartz, C. Giordano, N. A. Abumrad, and P. A. Grimaldi
Pharmacological activation of PPAR{beta} promotes rapid and calcineurin-dependent fiber remodeling and angiogenesis in mouse skeletal muscle
Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E297 - E304.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
F. Biscetti and R. Pola
Endothelial Progenitor Cells and Angiogenesis Join the PPARty
Circ. Res., July 3, 2008; 103(1): 7 - 9.
[Full Text] [PDF]

Home page
 Circ. Res.Home page
T. He, T. Lu, L. V. d'Uscio, C.-F. Lam, H.-C. Lee, and Z. S. Katusic
Angiogenic Function of Prostacyclin Biosynthesis in Human Endothelial Progenitor Cells
Circ. Res., July 3, 2008; 103(1): 80 - 88.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Han, J. D. Ritzenthaler, Y. Zheng, and J. Roman
PPAR{beta}/{delta} agonist stimulates human lung carcinoma cell growth through inhibition of PTEN expression: the involvement of PI3K and NF-{kappa}B signals
Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1238 - L1249.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
Y. Fan, Y. Wang, Z. Tang, H. Zhang, X. Qin, Y. Zhu, Y. Guan, X. Wang, B. Staels, S. Chien, et al.
Suppression of Pro-inflammatory Adhesion Molecules by PPAR-{delta} in Human Vascular Endothelial Cells
Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 315 - 321.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
D. Bishop-Bailey
Peroxisome Proliferator-Activated Receptor {beta}/{delta} Goes Vascular
Circ. Res., February 1, 2008; 102(2): 146 - 147.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. Panigrahy, A. Kaipainen, S. Huang, C. E. Butterfield, C. M. Barnes, M. Fannon, A. M. Laforme, D. M. Chaponis, J. Folkman, and M. W. Kieran
PPAR{alpha} agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition
PNAS, January 22, 2008; 105(3): 985 - 990.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
H. E. Hollingshead, R. L. Killins, M. G. Borland, E. E. Girroir, A. N. Billin, T. M. Willson, A. K. Sharma, S. Amin, F. J. Gonzalez, and J. M. Peters
Peroxisome proliferator-activated receptor- /{delta} (PPAR /{delta}) ligands do not potentiate growth of human cancer cell lines
Carcinogenesis, December 1, 2007; 28(12): 2641 - 2649.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. D. Brown and J. Plutzky
Peroxisome Proliferator Activated Receptors as Transcriptional Nodal Points and Therapeutic Targets
Circulation, January 30, 2007; 115(4): 518 - 533.
[Abstract] [Full Text] [PDF]


ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2006 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.