, For analysis, the mean number of branches per field was counted manually using . HUVEC proliferation was quantified by nuclear staining (see Supplementary Methods) and by measuring 5-Bromo-2?-deoxyuridine (BrdU) incorporation. For BrdU incorporation experiments, HUVEC were seeded in triplicate on gelatin-coated 96-well plates (7,000 cells/well) in experimental medium supplemented with 10% FBS. The following day, cells were incubated with 10 µM BrdU (Sigma-Aldrich, UK) and compounds of interest for 4 hours in experimental medium. Cells were then fixed in 4% PFA for 10 min. Incorporated BrdU was detected by immunofluorescence using an anti-BrdU antibody (BioLegend, USA) and DAPI nuclear stain. Cells were imaged using a Leica DMIRB inverted microscope (20x objective). BrdU and DAPI positive nuclei were counted using the Analyze Particles function on ImageJ software

, ON-TARGET plus SMART pool) (siRNA 1) or Sigma Aldrich (siRNA ID: SASI_Hs01_00231321) (siRNA 2), pre-complexed with Lipofectamine RNAiMAX lipid carrier (ThermoFisher Scientific; UK) according to the manufacturer's instructions. For all experiments, control wells/dishes containing cells transfected with non-coding control pool (10 nM) (Dharmacon; UK) were run in parallel. Plates were incubated for 24 h (37 °C/5% CO 2 ) before replacing the transfection medium with M199 growth medium. Cells were used for experiments 48 h post-transfection. Knockdown was assessed by RT-qPCR, immunocytochemistry and western blotting. Reverse transcription-quantitative pcR, Small interfering RNA (siRNA). HUVEC were transfected in Opti-MEM transfection medium containing carnitine palmitoyltransferase-1A (CPT1A) targeting siRNAs (10 nM) obtained from Dharmacon/GE healthcare

?. Sybr-®-premix-ex-taq and . Clontech, Protein samples (30 µg) were separated by SDS-PAGE at 150 V on 10% Tris-Glycine mini gels (ThermoFisher Scientific, UK) for 60-90 min. Resolved proteins were transferred to Hybond TM polyvinylidene difluoride (PVDF) membrane (0.45 µm; GE Healthcare; UK) by semi-dry transfer (0.8 mAmps/cm 2 ). Membranes were blocked (5% milk or 2.5% BSA; 1 h) and probed with primary antibodies at 4 °C overnight (anti-?-actin, Qiagen RNeasy Plus Mini Kit according to the manufacturer's instructions. Complementary DNA (cDNA) was synthesised by the reverse transcription (RT) of mRNA using Oligo(dT) priming and SuperScript TM II Reverse Transcriptase (ThermoFisher Scientific; UK). Quantitative PCR (qPCR), using both intercalator, vol.1, p.1000

, Cells were incubated in blocking buffer (3% BSA/1% goat serum; 40 min) prior to incubation with primary antibody (1% BSA/1% serum in PBS-Tween) at optimised concentrations (anti-SIRT1 1:250 (MERK Millipore; UK); anti-acetylated-FOXO1 1:100 (Santa Cruz Biotechnology; Germany); anti-CPT1A 1:300 (Cell Signaling Technology; UK)). Primary antibodies were detected with Alexa-Fluor 488 or Alexa-Fluor 594 secondary antibodies (1:1000 (ThermoFisher Scientific; UK)). Samples were then incubated with DAPI (1:5000 in TBS-Tween) for 5 min or coverslips were mounted using Fluoroshield DAPI-containing mounting medium (Sigma Aldrich; UK). Images were collected using either a DM4000B upright microscope (filter cubes A4 & L5 (Leica Microsystems)) or a Leica DMIRB inverted microscope (40x objective) controlled through Axiovision software version 4.8.2 (Carl Zeiss Ltd; UK), Band densities were semi-quantified by densitometry performed using ImageJ software and normalised to ?-actin loading control. immunocytochemistry. Cells were fixed in 4% PFA (10-15 min) and permeabilised in 0.1% Triton-X in PBS-Tween (15 min)

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