High glucose and hyperosmolarity increase heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) production in cultured human aortic endothelial cells

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Abstract
Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) has been shown to be a potent smooth muscle cell (SMC) mitogen and chemoattractant, and might be a candidate factor for the progression of atherosclerosis. We have investigated the effects of high glucose and hyperosmolarity on HB‐EGF production in cultured human aortic endothelial cells. Following the culture of the cells for 2 days with high concentrations of glucose or in the hyperosmolar conditions, we measured the content of HB‐EGF and the rate of production in the cells using a semi‐quantitative immunofluorescent technique and a metabolic radiolabelling method. With high glucose (16.6 mmol) and hyperosmolar conditions (glucose 5.5 mmol + mannitol 11.1 mmol or glucose 5.5 mmol + raffinose 11.1 mmol), the content of HB‐EGF was significantly increased and the metabolic rate was also significantly increased (more than a twofold increase, compared to that of 5.5 mmol glucose). In conclusion, conditions of high glucose or hyperosmolarity increase HB‐EGF production in human aortic endothelial cells. These results suggest that diabetic macroangiopathy might be attributed at least in part to HB‐EGF‐related vascular changes which may be induced by glucose.