S ubdermal plexus skin flaps, also known as local or random pattern flaps, may be used to reconstruct skin defects in dogs and cats when primary closure is not possible. Relatively simple to perform, an SPSF procedure may be preferred when a choice exists between that and a more advanced reconstructive technique, such as axial pattern flap or free-skin graft procedures. Unlike axial pattern flaps, SPSFs do not contain a specific or named direct cutaneous artery and instead derive their blood supply from the terminal branches of cutaneous trunci vessels in the subdermal plexus, which run from the base of the flap. However, in some anatomic areas, the wider the base of the SPSF, the greater the chance of accidentally incorporating part of an adjacent direct cutaneous artery. 1,2 Subdermal plexus skin flaps can be classified according to their location relative to the skin deficit Indications, complications, and outcomes associated with subdermal plexus skin flap procedures in dogs and cats: 92 cases (2000-2017

peroxisome proliferator activated receptor β/δ (PPARβ/δ) has pro-angiogenic functions, but whether PPARβ/δ modulates endothelial cell metabolism to support the dynamic phenotype remains to be established. This study characterised the metabolic response of HUVEC to the PPARβ/δ agonist, GW0742, and compared these effects with those induced by VEGF-A. In HUVEC monolayers, flux analysis revealed that VEGF-A promoted glycolysis at the expense of fatty acid oxidation (FAO), whereas GW0742 reduced both glycolysis and FAO. Only VEGF-A stimulated HUVEC migration and proliferation whereas both GW0742 and VEGF-A promoted tubulogenesis. Studies using inhibitors of PPARβ/δ or sirtuin-1 showed that the tubulogenic effect of GW0742, but not VEGF-A, was PPARβ/δand sirtuin-1-dependent. HUVEC were reliant on glycolysis and FAO, and inhibition of either pathway disrupted cell growth and proliferation. VEGF-A was a potent inducer of glycolysis in tubulogenic HUVEC, while FAO was maintained. In contrast, GW0742-induced tubulogenesis was associated with enhanced FAO and a modest increase in glycolysis. These novel data reveal a context-dependent regulation of endothelial metabolism by GW0742, where metabolic activity is reduced in monolayers but enhanced during tubulogenesis. These findings expand our understanding of PPARβ/δ in the endothelium and support the targeting of PPARβ/δ in regulating ec behaviour and boosting tissue maintenance and repair. Endothelial cells (ECs) lining normal vessels remain relatively quiescent, but retain the remarkable ability to acquire a highly active and dynamic phenotype following tissue injury or ischaemia 1. This is essential for angiogenesis, during which ECs sprout, migrate and proliferate to establish a new vascular network. Cells undergoing such rapid and dynamic alterations in growth and proliferation are known to exhibit significant alterations in their metabolism 2 , so interest in targeting master metabolic regulators, or metabolic pathways directly, to influence EC behaviour is growing 3,4. While the importance of various metabolic pathways for sustaining angiogenic behaviour is increasingly recognised 3,5 , knowledge of how ECs adapt their metabolism in response to extrinsic signals is particularly lacking. Exposure to vascular endothelial growth factor A (VEGF-A), a well-studied angiogenic growth factor, is known to increase glycolytic flux in ECs, in part through stimulation of the phosphoinositide 3-kinase (PI3-K)/ Akt signalling pathway and increased activity of key enzymes in the glycolytic cascade 6. Characterisation of the metabolic response of ECs to other established and putative angiogenic factors, and the functional importance of these changes, has not been addressed to date. The peroxisome proliferator activated receptor β/δ (PPARβ/δ) nuclear receptor has been identified as a facilitator of the angiogenic response and synthetic PPARβ/δ agonists generally exhibit pro-angiogenic activity 7-10. PPARβ/δ controls the expression of multiple genes linked to the regulation of glucose ...