Sohni Ria Bhalla

Abstract In peripheral arterial disease (PAD) anti-angiogenic VEGF-A165b, isoform overexpression in monocytes contributes to impaired collateralisation. Serine-arginine protein-kinase-1 (SRPK1) regulates VEGF splicing. To determine whether SRPK1 controlled monocytic VEGF, impairing collateralisation, we investigated SRPK1 inhibition and monocyte-specific knockout in mouse models of and in human monocytes from PAD.

Abstract In peripheral arterial disease (PAD) vascular insufficiency and reduced blood flow results from overexpression of the anti-angiogenic splice isoform of VEGF-A, VEGF-A165b, in monocytes. Serine-arginine protein-kinase 1 (SRPK1) has been shown to regulate VEGF splicing.

Abstract VEGF-A splicing has been shown to be regulated in cancer and epithelial cells by phosphorylation of serine/arginine splicing factor 1 (SRSF1) by serine-arginine protein kinase 1 (SRPK1). In these cell types inhibition of SRPK1 switches splicing to the anti-angiogenic VEGF-A isoforms. In peripheral arterial disease (PAD) the anti-angiogenic isoform of VEGF-A, VEGF-A165b, is overexpressed in circulating monocytes.