High glucose and hyperosmolarity increase heparin-binding epidermal growth factor-like growth factor (HB-EGF) production in cultured human aortic endothelial cells.
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.
Asakawa
H
H
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Miyagawa
J
J
Higashiyama
S
S
Goishi
K
K
Hanafusa
T
T
Kuwajima
M
M
Taniguchi
N
N
Matsuzawa
Y
Y
D001011:Aorta / Q000187:drug effects; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D005947:Glucose / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D004815:Epidermal Growth Factor; D005947:Glucose