CD248 (Endosialin) is a type 1 membrane protein involved in developmental and pathological angiogenesis through its expression on pericytes and regulation of PDGFRβ signalling. Here we explore the function of CD248 in skeletal muscle angiogenesis. Two distinct forms of capillary growth (splitting and sprouting) can be induced separately by increasing microcirculatory shear stress (chronic vasodilator treatment) or by inducing functional overload (extirpation of a synergistic muscle). We show that CD248 is present on pericytes in muscle and that CD248-/- mice have a specific defect in capillary sprouting. In contrast, splitting angiogenesis is independent of CD248 expression. Endothelial cells respond to pro-sprouting angiogenic stimulus by up-regulating gene expression for HIF1α, angiopoietin 2 and its receptor TEK, PDGF-B and its receptor PDGFRβ; this response did not occur following a pro-splitting angiogenic stimulus. In wildtype mice, defective sprouting angiogenesis could be mimicked by blocking PDGFRβ signalling using the tyrosine kinase inhibitor Imatinib mesylate. We conclude that CD248 is required for PDGFRβ-dependant capillary sprouting but not splitting angiogenesis, and identify a new role for CD248 expressed on pericytes in the early stages of physiological angiogenesis during muscle remodelling.

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A 68-year-old woman presented to the emergency department, with an abscess in the right upper anterior abdominal wall. She had a medical history of an open cholecystectomy 20 years prior, diabetes, obesity and a laparotomy for perforated sigmoid diverticular disease complicated by a large parastomal hernia. CT revealed this subcutaneous abscess to track intra-abdominally through the liver and communicate with the gallbladder fossa. The abscess was incised and drained. The wound initially drained pus, and then bile. Magnetic resonance cholangiopancreatogram (MRCP) demonstrated a remnant gallbladder containing 2 gallstones, a cholecystocutaneous fistula, portal vein thrombosis and cavernous transformation of the bile duct. The patient improved and was discharged. The patient's case history and imaging were discussed with the tertiary referral centre, in a multidisciplinary team. After an extensive and balanced discussion, the patient declined a completion cholecystectomy and continues to have occasional discharge from the fistula in her right upper quadrant.

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