OBJECTIVES: Angiogenesis plays a critical role in SSc ( @entity2631 ). The aim of this study was to examine the expression of growth-regulated protein-y (Gro-y/ @entity10150 ), @entity25296 ( @entity25296 / @entity25296 ) and their receptor @entity7416 in endothelial cells (ECs) isolated from SSc skin and determine whether these cells mount an angiogenic response towards pro-angiogenic chemokines. The downstream signalling pathways as well as the pro-angiogenic transcription factor inhibitor of DNA-binding protein 1 ( @entity13863 ) were also examined. METHODS: Skin biopsies were obtained from @entity1 with dcSSc. ECs were isolated via magnetic positive selection. Angiogenesis was measured by EC chemotaxis assay. RESULTS: Gro-y/ @entity10150 and @entity25296 / @entity25296 were minimally expressed in both skin types but elevated in SSc serum. Pro-angiogenic chemokine mRNA was greater in SSc ECs than in normal ECs. SSc ECs did not migrate to @entity7 ( @entity7 ), Gro-y/ @entity10150 , @entity25296 / @entity25296 or @entity6332 . The signalling pathways stimulated by these chemokines were also dysregulated. @entity13863 mRNA in SSc ECs was lower compared with normal ECs, and overexpression of @entity13863 in SSc ECs increased their ability to migrate towards @entity7 and @entity6332 . CONCLUSION: Our results show that SSc ECs are unable to respond to pro-angiogenic chemokines despite their increased expression in serum and ECs. This might be due to the differences in the signalling pathways activated by these chemokines in normal vs SSc ECs. In addition, the lower expression of @entity13863 also decreases the angiogenic response. The inability of pro-angiogenic chemokines to promote EC migration provides an additional mechanism for the impaired angiogenesis that characterizes SSc.

XXXX dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity7 :: ('7422', 'Gene') :: ['vascular endothelial growth factor', 'VEGF'] @entity2631 :: ('MESH:D012594', 'Disease') :: ['scleroderma'] @entity6332 :: ('58191', 'Gene') :: ['CXCL16'] @entity25296 :: ('6372', 'Gene') :: ['CXCL6', 'GCP-2', 'granulocyte chemotactic protein 2'] @entity7416 :: ('3579', 'Gene') :: ['CXCR2'] @entity13863 :: ('3397', 'Gene') :: ['Id-1'] @entity10150 :: ('2921', 'Gene') :: ['CXCL3']
@entity2631 :: (MESH:D012594,Disease) :: ['Scleroderma']
