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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4468-4475. Prepublished online as a Blood First Edition Paper on December 10, 2008; DOI 10.1182/blood-2008-07-171108. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-171108v1 113/18/4468    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 Kärkkäinen, A.-M. Articles by Ylä-Herttuala, S. Search for Related Content PubMed PubMed Citation Articles by Kärkkäinen, A.-M. Articles by Ylä-Herttuala, S. Related Collections Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Vascular endothelial growth factor-D transgenic mice show enhanced blood capillary density, improved postischemic muscle regeneration, and increased susceptibility to tumor formation Anna-Mari Kärkkäinen1, Antti Kotimaa1, Jenni Huusko1, Ivana Kholova1, Suvi Elina Heinonen1, Anna Stefanska1, Marike Hinke Dijkstra1, Hanna Purhonen1, Eveliina Hämäläinen1, Petri Ilmari Mäkinen1, Mikko Petri Turunen1, and Seppo Ylä-Herttuala1 1 A.I. Virtanen Institute, Department of Biotechnology and Molecular Medicine, University of Kuopio, Kuopio, Finland Vascular endothelial growth factor-D (VEGF-D) has angiogenic and lymphangiogenic activity, but its biologic role has remained unclear because knockout mice showed no clear phenotype. Transgenic (TG) mice expressing the mature form of human VEGF-D (hVEGF-D) were produced by lentiviral (LV) transgenesis using the perivitelline injection method. Several viable founders showed a macroscopically normal phenotype and the transgene transmitted through germ line. Expression of hVEGF-D mRNA was high in skeletal muscles, skin, pancreas, heart, and spleen. A significant increase was found in capillary density of skeletal muscles and myocardium, whereas no changes were observed in lymphatic capillary density. After induction of hindlimb ischemia, the TG mice showed enhanced capacity for muscle regeneration. However, on aging the TG mice had significantly increased mortality from malignant tumors, of which half were breast adenocarcinomas characterized with the absence of periductal muscle cells. Some tumors metastasized into the lungs. In addition, lung and skin tumors were found, but no blood- or lymphatic vessel–derived malignancies were detected. We conclude that in mice hVEGF-D is an angiogenic factor associated with improved muscle regeneration after ischemic injury but also with increased incidence of tumor formation with a preference for mammary gland tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Lymphangiogenesis factors: a target for therapy? Arjan W. Griffioen Blood 2009 113: 4135-4136. [Full Text] [PDF] This article has been cited by other articles: A. W. Griffioen Lymphangiogenesis factors: a target for therapy? Blood, April 30, 2009; 113(18): 4135 - 4136. [Full Text] [PDF]

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