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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 (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 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 Karkkainen, A.-M. Articles by Yla-Herttuala, S. Search for Related Content PubMed PubMed Citation Articles by Karkkainen, A.-M. Articles by Yla-Herttuala, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2008 Accepted November 14, 2008 VEGF-D transgenic mice show enhanced blood capillary density, improved post-ischemic muscle regeneration and increased susceptibility to tumor formation Anna-Mari Karkkainen, Antti Kotimaa, Jenni Huusko, Ivana Kholova, Suvi Elina Heinonen, Anna Stefanska, Marike Hinke Dijkstra, Hanna Purhonen, Eveliina Hamalainen, Petri Ilmari Makinen, Mikko Petri Turunen, and Seppo Yla-Herttuala* Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland * Corresponding author; email: seppo.ylaherttuala{at}uku.fi. Vascular endothelial growth factor-D (VEGF-D) has angiogenic and lymphangiogenic activity, but its biological role has remained unclear since knockout mice showed no clear phenotype. Transgenic (TG) mice expressing mature form of human VEGF-D (hVEGF-D) were produced via lentiviral (LV) transgenesis using perivitelline injection method. Several viable founders showed a macroscopically normal phenotype and the transgene transmitted through germline. 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, upon 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 lungs. Also, lung and skin tumors were found, but no blood- and 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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