TY - JOUR T1 - Increased plasma levels of the VEGF<sub>165</sub>b splice variant are associated with the severity of nailfold capillary loss in systemic sclerosis JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1425 LP - 1427 DO - 10.1136/annrheumdis-2012-203183 VL - 72 IS - 8 AU - Mirko Manetti AU - Serena Guiducci AU - Eloisa Romano AU - Silvia Bellando-Randone AU - Gemma Lepri AU - Cosimo Bruni AU - Maria Letizia Conforti AU - Lidia Ibba-Manneschi AU - Marco Matucci-Cerinic Y1 - 2013/08/01 UR - http://ard.bmj.com/content/72/8/1425.abstract N2 - In systemic sclerosis (SSc), Raynaud's phenomenon is the earliest clinical manifestation paralleled by nailfold capillaroscopic alterations that may occur months or even years before the onset of fibrosis.1 This evidence suggests a crucial role of microangiopathy characterised by a progressive loss of capillaries with the formation of avascular areas.1 ,2 Consequent chronic tissue hypoxia leads to skin ulcers and gangrene that heavily burden patients’ quality of life.1 ,2 Vascular endothelial growth factor-A (VEGF-A) is overexpressed in SSc skin, and increased circulating levels of VEGF-A correlate with the severity of nailfold capillary loss.2–4 It has been demonstrated that the VEGF-A primary transcript can be alternatively spliced in its terminal exon, producing two distinct mRNA splice variants that are translated to the proangiogenic VEGF165 and antiangiogenic VEGF165b isoforms.5 These two isoforms bind to the tyrosine kinase receptor VEGFR-2 with the same affinity, but binding of VEGF165b results in an insufficient tyrosine phosphorylation/activation of VEGFR-2 and incomplete or transient downstream signalling, which lead to an impaired angiogenic response.5 ,6 Recently, we have provided the first evidence that dermal expression and plasma levels of VEGF165b are raised in SSc patients, and VEGF165b overexpression prevents SSc dermal microvascular endothelial … ER -