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Blood, 1 January 2007, Vol. 109, No. 1, pp. 122-129. Prepublished online as a Blood First Edition Paper on September 21, 2006; DOI 10.1182/blood-2006-07-031773. This Article Full Text (PDF) All Versions of this Article: blood-2006-07-031773v1 109/1/122    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lucerna, M. Articles by Biessen, E. Search for Related Content PubMed PubMed Citation Articles by Lucerna, M. Articles by Biessen, E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 7, 2006 Accepted August 10, 2006 Vascular endothelial growth factor-A induces plaque expansion in ApoE knockout mice by promoting de novo leukocyte recruitment Markus Lucerna, Alma Zernecke, Ramon de Nooijer, Saskia de Jager, Ilze Bot, Christian van der Lans, Ivana Kholova, Elisa Liehn, Theo van Berkel, Seppo Yla-Herttuala, Christian Weber, and Erik Biessen* Leiden University, Leiden, The Netherlands / Medical University Vienna, Vienna, Austria Institute for Molecular Cardiovascular Research, University Hospital, Aachen, Germany Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands A.I. Virtanen Institute of Molecular Sciences, University of Kuopio, Kuopio, Finland * Corresponding author; email: biessen{at}chem.leidenuniv.nl. Vascular endothelial growth factor-A is widely used in clinical trials for the treatment of cardiac ischemia. VEGF-A was recently suggested to act pro-inflammatory, which could aggravate adjacent atherogenesis in VEGF-A based therapy. To asssess potential bystander effects, VEGF-A was focally overexpressed in advanced atherosclerotic plaques in ApoE-/- mice. Sheer-induced carotid artery plaques were transluminally incubated with Ad.hVEGF-A leading to neointimal overexpression of VEGF-A. Ad.hVEGF-A treatment of pre-existing lesions was seen to promote plaque expansion, with a concomitant increase in macrophage and lipid content, whereas it lowered plaque collagen content. In general, Ad.hVEGF-A treated plaques displayed a more vulnerable phenotype. VEGF-A overexpression was not accompanied by increased microvessel development in the neointima, suggesting that VEGF-A destabilizes atherosclerotic plaques through an angiogenesis-independent mechanism. Intravital microscopy confirmed that treatment with Ad.hVEGF-A led to an increased monocyte adhesion, which was mediated by a VCAM-1/PECAM-1-dependent pathway. VEGF-A indeed induced a differential expression of VCAM-1 and PECAM-1 in endothelial cells. Our data underline the importance of regular monitoring stenotic vessels adjacent to the site of VEGF-A application. We propose that VCAM-1/PECAM-1-directed co-therapy may be an efficient strategy to prevent adverse bystander effects of focal VEGF-A therapy in patients suffering from cardiovascular disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: VEGF therapy: risky business for established plaques? Alexandra Kadl and Norbert Leitinger Blood 2007 109: 2-3. [Full Text] [PDF] This article has been cited by other articles: Q. Hao, L. Wang, and H. Tang Vascular endothelial growth factor induces protein kinase D-dependent production of proinflammatory cytokines in endothelial cells Am J Physiol Cell Physiol, April 1, 2009; 296(4): C821 - C827. [Abstract] [Full Text] [PDF] F. Sanada, Y. Taniyama, J. Azuma, K. Iekushi, N. Dosaka, T. Yokoi, N. Koibuchi, H. Kusunoki, Y. Aizawa, and R. Morishita Hepatocyte Growth Factor, but not Vascular Endothelial Growth Factor, Attenuates Angiotensin II-Induced Endothelial Progenitor Cell Senescence Hypertension, January 1, 2009; 53(1): 77 - 82. [Abstract] [Full Text] [PDF] R. L. Nachman and S. Rafii Platelets, Petechiae, and Preservation of the Vascular Wall N. Engl. J. Med., September 18, 2008; 359(12): 1261 - 1270. [Full Text] [PDF] O. V. Oskolkova, T. Afonyushkin, A. Leitner, E. von Schlieffen, P. S. Gargalovic, A. J. Lusis, B. R. Binder, and V. N. Bochkov ATF4-dependent transcription is a key mechanism in VEGF up-regulation by oxidized phospholipids: critical role of oxidized sn-2 residues in activation of unfolded protein response Blood, July 15, 2008; 112(2): 330 - 339. [Abstract] [Full Text] [PDF] F. Addabbo, F. Mallamaci, D. Leonardis, R. Tripepi, G. Tripepi, M. S. Goligorsky, and C. Zoccali Searching for biomarker patterns characterizing carotid atherosclerotic burden in patients with reduced renal function Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3521 - 3526. [Abstract] [Full Text] [PDF] A. D. Hauer, G. H.M. van Puijvelde, N. Peterse, P. de Vos, V. van Weel, E. J.A. van Wanrooij, E. A.L. Biessen, P. H.A. Quax, A. G. Niethammer, R. A. Reisfeld, et al. Vaccination Against VEGFR2 Attenuates Initiation and Progression of Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 2050 - 2057. [Abstract] [Full Text] [PDF]

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