Heparanase secretion and reuptake into ECs. RAOEC (passage 5–8) and RHMEC (passage 5–8) were incubated in either 5.5 (normal glucose control; Con) or 25 mM (HG) glucose for 30 min. Incubation medium was collected and used to determine latent (HepL) and active (HepA) heparanase secretion, n = 6–7 (A and B), **P < 0.01 compared to Con. RAOEC (C) and RHMEC (D) were incubated in 25 (HG) mM glucose for 30 or 60 min. Cell lysates and incubation medium were used to determine the intracellular and extracellular content of HepL and HepA, n = 5, **P < 0.01. RAOEC and RHMEC were incubated with normal glucose and 500 ng/mL myc-HepL. Cell lysates were collected at indicated time points to measure the uptake of myc-HepL and its conversion to HepA, n = 6 (E), **P < 0.01 compared to RHMEC.