Overexpression of VEGF165b, an Inhibitory Splice Variant of Vascular Endothelial Growth Factor, Leads to Insufficient Angiogenesis in Patients With Systemic Sclerosis

摘要: Rationale: Systemic sclerosis (SSc) is characterized by widespread microangiopathy, fibrosis, and autoimmunity. Despite the lack of angiogenesis, expression vascular endothelial growth factor A (VEGF) was shown to be upregulated in SSc skin circulation; however, previous studies did not distinguish between proangiogenic VEGF165 antiangiogenic VEGF165b isoforms, which are generated alternative splicing terminal exon VEGF pre-RNA. Objective: We investigated whether isoform could altered circulation patients with SSc. Methods Results: Here, we show that endogenous splice variant selectively overexpressed at both mRNA protein levels skin. Elevated correlated increased profibrotic transforming factor-β1 serine/arginine 55 keratinocytes, fibroblasts, cells, perivascular inflammatory cells. Circulating were significantly higher than control subjects. Microvascular cells (MVECs) isolated from expressed released healthy MVECs. Transforming In MVECs, receptor-2 overexpressed, but its phosphorylation impaired. Recombinant SSc-MVEC–conditioned medium inhibited VEGF165-mediated capillary morphogenesis The addition anti-VEGF165b blocking antibodies abrogated effect medium. Capillary severely impaired MVECs ameliorated treatment recombinant antibodies. Conclusions: SSc, a switch isoforms may have crucial role insufficient angiogenic response chronic ischemia. # Novelty Significance {#article-title-37}