In vitro cultured rat islets express genes that both prevent and promote angiogenesis.
BACKGROUND
Endogenous pancreatic islets are supported by a dense sinusoidal capillary system which is disrupted following isolation and culture in vitro. A rapid and accurate revascularization is therefore crucial for the survival and functioning of the transplanted islet. Although a blood flow is established in islet grafts within 1-2 weeks, these islets show poor development of intra-islet capillaries. To improve the revascularization process and the arrangement of the new blood vessels, islet production of the factors governing these processes needs to be further characterized.


OBJECTIVE
To study the expression of factors which regulate angiogenesis in cultured rat islets.


METHODS
Rat islets were isolated and cultured for one week. After 6 hours of exposure to normoxic (21% O2) or hypoxic (1% O2) conditions, mRNA expression was evaluated by the GEArray Angiogenesis 1 and 2 systems. The expression of the vascular endothelial growth factor (VEGF), the tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 1 (Tie1) and acidic fibroblast growth factor (aFGF), was further evaluated by semi-quantitative RT-PCR.


RESULTS
We found the expression of 19 genes that code for factors either promoting or preventing angiogenesis. Only VEGF and Tie1 were upregulated in response to hypoxia.


CONCLUSIONS
Hypoxia-induced islet vascularization may involve VEGF and Tie-induced signaling events. The results also show that cultured islets express genes which prevent angiogenesis concurrently with genes coding for factors stimulating angiogenesis. The balance between these factors is probably of vital importance for the revascularization process in transplanted islets. Thus, pharmacologic or genetic attenuation of islet-derived angiostatic factors may prove beneficial in promoting islet revascularization in future transplantation trials.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. nils.welsh@medcellbiol.uu.se
Linda
L
Tillmar
Nils
N
Welsh
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D007515:Islets of Langerhans / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D012333:RNA, Messenger