angiogenesis; trichostatin A; suberoylanilide hydroxamic acid; VEGF; neuropilin-1; semaphorin III
Abstract :
[en] Angiogenesis is a complex biological process involving the coordinated modulation of many genes. Histone deacetylases (HDAC) are a growing family of enzymes that mediate the availability of chromatin to the transcriptional machinery. Trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA), two HDAC inhibitors known to relieve gene silencing, were evaluated as potential antiangiogenic agents. TSA and SAHA were shown to prevent vascular endothelial growth factor (VEGF)-stimulated human umbilical cord endothelial cells (HUVEC) from invading a type I collagen gel and forming capillary-like structures. SAHA and TSA inhibited the VEGF-induced formation of a CD31-positive capillary-like network in embryoid bodies and inhibited the VEGF-induced angiogenesis in the CAM assay. TSA also prevented, in a dose-response relationship, the sprouting of capillaries from rat aortic rings. TSA inhibited in a dose-dependent and reversible fashion the VEGF-induced expression of VEGF receptors, VEGFR1, VEGFR2, and neuropilin-1. TSA and SAHA upregulated the expression by HUVEC of semaphorin III, a recently described VEGF competitor, at both mRNA and protein levels. This effect was specific to endothelial cells and was not observed in human fibroblasts neither in vascular smooth muscle cells. These observations provide a conspicuous demonstration that HDAC inhibitors are potent anti-angiogenic factors altering VEGF signaling.
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Colige, Alain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Clausse, Nathalie
Blacher, Silvia ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Verdin, Eric
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Nusgens, Betty ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
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