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Archives of cardiovascular diseases
Volume 102, n° S1
page 41 (mars 2009)
Doi : 10.1016/S1875-2136(09)72225-9
Themes et posters

D015 Aldosterone plays a pro-angiogenic role by enhancing VEGF-A production in immune cells
 

C. Walczak, F. Gaignier, G. Bello, A. GILET, S. Thornton, P. Lacolley, A. Ropars
U961 Inserm, Vandœuvre-lès-Nancy, France 

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Background and aim

VEGF-A has been described to be an important pro-angiogenic factor. Immune cells are intimately involved in tissue repair and neovascularisation notably by their capacity to secrete VEGF-A. Moreover, these cells possess mineralocorticoid receptors. The present study was designed to investigate whether aldosterone (Aldo) was able to regulate VEGF-A production of immune cells.

Methods

HL-60 (progranulocytic) and THP-1 (promonocytic) cell lines and human blood neutrophils and monocytes were incubated for different times with Aldo (10-7, 10-8, 10-9 M). Total cellular RNA extraction, submitted to reverse transcription and real time quantitative PCR was used to study VEGF-A mRNA expression. Cell supernatants were collected and ELISA tests were performed to analyse VEGF-A protein excretion.

Results

All four cell types increased their VEGF-A mRNA and protein production. VEGF-A mRNA expression increased from 30 mn and time for maximal expression depended on cell type: 30 mn for HL-60 and THP-1 cells, and for blood neutrophils3 hours after Aldo addition. ELISA tests showed increased excretion of VEGF-A proteins after 24 hours of Aldo contact for all four cell types. Western-blotting performed with HL-60 and THP-1 cells showed that ERK1/2 and p38 pathways are stimulated by Aldo. ERK1/2, p38 and PI3kinase transduction signal inhibitors decreased this immune cell activation orchestrated by Aldo.

Conclusion

We have demonstrated that Aldo is able to increase VEGF-A production of phagocytic cells such as neutrophils and monocytes. This phenomenon is PI3K, ERK1/2 and p38 dependent. These cells play an important role in tissue healing notably by their capacity to degrade dead cells and to secrete pro-angiogenic factors such as VEGF-A in situ. It appears that Aldo could play an important role in this neovascularisation process by favouring cell proliferation and tissue building.

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