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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 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 Citation Map 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. A. L. Search for Related Content PubMed PubMed Citation Articles by Lucerna, M. Articles by Biessen, E. A. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment Markus Lucerna1,4, Alma Zernecke2, Ramon de Nooijer1, Saskia C. de Jager1, Ilze Bot1, Christian van der Lans1, Ivana Kholova3, Elisa A. Liehn2, Theo J. C. van Berkel1, Seppo Yla-Herttuala3, Christian Weber2, and Eric A. L. Biessen1, 1 Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands; 2 Institute for Molecular Cardiovascular Research, University Hospital, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany; 3 A. I. Virtanen Institute of Molecular Sciences, University of Kuopio, Finland; and 4 Medical University Vienna, Center of Biomolecular Medicine and Pharmacology, Department of Vascular Biology and Thrombosis Research, Vienna, Austria Vascular endothelial growth factor-A is widely used in clinical trials for the treatment of cardiac ischemia. VEGF-A was recently suggested to act in a proinflammatory manner, which could aggravate adjacent atherogenesis in VEGF-A–based therapy. To assess 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 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 of stenotic vessels adjacent to the site of VEGF-A application. We propose that VCAM-1/PECAM-1–directed cotherapy may be an efficient strategy to prevent 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. 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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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